Safety Studies of a Recently Developed Microbicidal Contraceptive Gel (UniPron) in Female Baboons (Papio Anubis)

African Journal of Reproductive Health. Dec, 2009  |  Pubmed ID: 20690277

To identify any toxicity on the vaginal epithelium, liver and kidney following UIniPron administration, ten healthy female olive baboons (Papio anubis) of reproductive age and of proven fertility were used. Five baboons were each treated with 15 g of UniPron intravaginally twice a week for 20-weeks and venous blood collected before and after each treatment. Venous blood was collected from five control animals as in the experimental females, but these control animals were not given any treatment. The endpoints that were evaluated included clinical chemistry profiles on kidney and liver functions and vaginal histopathology. Female baboons treated with 15 g of UniPron intravaginally showed no detectable adverse effects on clinical chemistry profiles investigated and vaginal histopathology. Repeated intravaginal exposure of female baboons to UniPron did not induce detectable vaginal irritation and there were no detectable histological changes. We conclude that administration of UniPron into baboon vagina did not cause any detectable toxicity.

In Vitro Screening of Metabolic Clearance Using Two Concentration Points

Drug Metabolism Letters. Dec, 2010  |  Pubmed ID: 20690899

For high throughput screens, the quickest methodology possible is desirable, but a substantial amount of potentially useful information is lacking since most screens for metabolic stability are conducted at one concentration, and sometimes at one time point. Information that would benefit projects during the discovery phase are to know the metabolic rate linearity (K(m) value) and projected hepatic clearance (CL(h) value), which is possible by the addition of one more concentration. This study used the FDA-preferred probe cytochrome P450 substrates to determine K(m), V(max), and CL(int) values. The results showed that compounds with relatively high metabolic rates produced more accurate and reproducible results that match well with predicted K(m) values according to the FDA. On the other hand, compounds with relatively low metabolic rates yielded more variable results. Thus, the use of two substrate concentrations should be useful with screening assays for assessing the kinetic values for other compounds.

The Xanthomonas Citri Effector Protein PthA Interacts with Citrus Proteins Involved in Nuclear Transport, Protein Folding and Ubiquitination Associated with DNA Repair

Molecular Plant Pathology. Sep, 2010  |  Pubmed ID: 20696004

Xanthomonas axonopodis pv. citri utilizes the type III effector protein PthA to modulate host transcription to promote citrus canker. PthA proteins belong to the AvrBs3/PthA family and carry a domain comprising tandem repeats of 34 amino acids that mediates protein-protein and protein-DNA interactions. We show here that variants of PthAs from a single bacterial strain localize to the nucleus of plant cells and form homo- and heterodimers through the association of their repeat regions. We hypothesize that the PthA variants might also interact with distinct host targets. Here, in addition to the interaction with alpha-importin, known to mediate the nuclear import of AvrBs3, we describe new interactions of PthAs with citrus proteins involved in protein folding and K63-linked ubiquitination. PthAs 2 and 3 preferentially interact with a citrus cyclophilin (Cyp) and with TDX, a tetratricopeptide domain-containing thioredoxin. In addition, PthAs 2 and 3, but not 1 and 4, interact with the ubiquitin-conjugating enzyme complex formed by Ubc13 and ubiquitin-conjugating enzyme variant (Uev), required for K63-linked ubiquitination and DNA repair. We show that Cyp, TDX and Uev interact with each other, and that Cyp and Uev localize to the nucleus of plant cells. Furthermore, the citrus Ubc13 and Uev proteins complement the DNA repair phenotype of the yeast Deltaubc13 and Deltamms2/uev1a mutants, strongly indicating that they are also involved in K63-linked ubiquitination and DNA repair. Notably, PthA 2 affects the growth of yeast cells in the presence of a DNA damage agent, suggesting that it inhibits K63-linked ubiquitination required for DNA repair.

Retinal and Ocular Toxicity in Ocular Application of Drugs and Chemicals--part II: Retinal Toxicity of Current and New Drugs

Ophthalmic Research. 2010  |  Pubmed ID: 20699625

Retinal pharmacotherapy has gained great importance for the treatment of various retinal diseases. An increasing number of drugs have been constantly released into the market, especially for wet age-related macular disease and diabetic macular edema. In this review, the issues concerning the toxicity of current and new classes of drugs are discussed.

Socioeconomic Status and the Brain: Mechanistic Insights from Human and Animal Research

Nature Reviews. Neuroscience. Sep, 2010  |  Pubmed ID: 20725096

Human brain development occurs within a socioeconomic context and childhood socioeconomic status (SES) influences neural development--particularly of the systems that subserve language and executive function. Research in humans and in animal models has implicated prenatal factors, parent-child interactions and cognitive stimulation in the home environment in the effects of SES on neural development. These findings provide a unique opportunity for understanding how environmental factors can lead to individual differences in brain development, and for improving the programmes and policies that are designed to alleviate SES-related disparities in mental health and academic achievement.

[An Exceptional Hepatic Tumor]

La Tunisie Médicale. Dec, 2010  |  Pubmed ID: 21136369

Hepatic localization of non Hodgkin's lymphoma is generally secondary. Primary localizations are rare.

Immune Thrombocytopenic Purpura Associated with Brucellosis. Case Report and Review of the Literature

Le Journal Médical Libanais. The Lebanese Medical Journal. Oct-Dec, 2010  |  Pubmed ID: 21409948

A case of severe thrombocytopenic purpura as the sole manifestation of brucellosis in an eight-year-old boy is presented. Clinical examination revealed mucosal hemorrhages and splenomegaly. The initial diagnosis was immune thrombocytopenic purpura (ITP) and he received intravenous gamma globulins and steroids with good hematologic and clinical response. His brucella agglutination titer was positive and he received treatment with intravenous gentamicin and oral co-trimoxazole with good response. Although mild hematologic manifestations can be encountered in brucellosis, severe thrombocytopenia is rare. Prompt recognition of this association is essential for early therapy. A brief review of thrombo-cytopenic purpura associated with brucellosis is presented.

Microbial Etiology of Febrile Neutropenia

Indian Journal of Hematology & Blood Transfusion : an Official Journal of Indian Society of Hematology and Blood Transfusion. Jun, 2010  |  Pubmed ID: 21629636

Bacterial and fungal infections are a major cause of morbidity and mortality among neutropenic patients. The choice of empiric antimicrobial regimen is based on susceptibility pattern of locally prevalent pathogens. From 64 febrile neutropenic patients with clinical sepsis, blood and other appropriate clinical specimens were processed to determine bacterial and fungal spectrum and their antimicrobial susceptibility pattern. Risk factors for developing sepsis were determined by case-control study. 68 organisms were recovered. Fifteen (22.05%) were Gram-positive cocci with predominance of methicillin Sensitive S. aureus (10.29%), 47 (69.11%) were Gram-negative rods with predominance of Klebsiella pneumoniae (30.88%) and four were Non albicans Candida. 81% and 60% of Klebsiella and E. coli were ESBL producers. All species of Candida were sensitive to amphoterecin B and voriconazole. Duration and extent of neutropenia, chemotherapy, immunosuppressive therapy, altered mucosal barriers and presence of central venous lines were statistically significant risk factors for developing sepsis. Gram-negative bacteria were the predominant isolates. The choice of therapy in neutropenic patients should be formulated based on local spectrum of microbes and local and regional resistance patterns.

Gestational Weight Gain and Birthweight

Irish Medical Journal. Nov-Dec, 2010  |  Pubmed ID: 21560497

Nissen Fundoplication for the Treatment of Gastroesophageal Reflux Disease in Patients with Chagas Disease Without Achalasia

Revista Do Instituto De Medicina Tropical De São Paulo. Mar-Apr, 2010  |  Pubmed ID: 20464134

Quantitative Evaluation of Experimental Choroidal Neovascularization by Confocal Scanning Laser Ophthalmoscopy: Fluorescein Angiogram Parallels Heparan Sulfate Proteoglycan Expression

Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas / Sociedade Brasileira De Biofísica ... [et Al.]. Jul, 2010  |  Pubmed ID: 20464343

The objective of the present study was to develop a quantitative method to evaluate laser-induced choroidal neovascularization (CNV) in a rat model using Heidelberg Retina Angiograph 2 (HRA2) imaging. The expression of two heparan sulfate proteoglycans (HSPG) related to inflammation and angiogenesis was also investigated. CNV lesions were induced with argon laser in 21 heterozygous Zucker rats and after three weeks a fluorescein angiogram and autofluorescence exams were performed using HRA2. The area and greatest linear dimension were measured by two observers not aware of the protocol. Bland-Altman plots showed agreement between the observers, suggesting that the technique was reproducible. After fluorescein angiogram, HSPG (perlecan and syndecan-4) were analyzed by real-time RT-PCR and immunohistochemistry. There was a significant increase in the expression of perlecan and syndecan-4 (P < 0.0001) in retinas bearing CNV lesions compared to control retinas. The expression of these two HSPG increased with increasing CNV area. Immunohistochemistry demonstrated that the rat retina damaged with laser shots presented increased expression of perlecan and syndecan-4. Moreover, we observed that the overexpression occurred in the outer layer of the retina, which is related to choroidal damage. It was possible to develop a standardized quantitative method to evaluate CNV in a rat model using HRA2. In addition, we presented data indicating that the expression of HSPG parallels the area of CNV lesion. The understanding of these events offers opportunities for studies of new therapeutic interventions targeting these HSPG.

Significance of Differential Metal Loads in Normal Versus Cancerous Cadaver Tissues - Biomed 2010

Biomedical Sciences Instrumentation. 2010  |  Pubmed ID: 20467115

The bodys elemental/ metal loads are known to exert essential influence in maintaining normal and abnormal metabolism leading to eventual pathology of some forms of cancer phenotypes. Accumulation of potentially toxic or nonessential trace metals has been observed but not highly noted as an active factor in toxicogenesis and in the development of many diseases including cancers. The compositional balance and distribution of trace metals in various body tissues are essential key players in homeostasis in life. To this end the etiology of diseases including cancer has been linked with the accumulation of potentially toxic or nonessential trace metals. However, scarce literature / experimental evidence exist as a scientific proof that metal concentrations play important role in the etiology and development of cancer phenotypes. The aim of this study was to investigate the differential relationship of metal concentrations and profiles in cancer and normal tissues from cadavers of humans. The originated hypothesis was that elemental / metal concentrations and profiles seen in post mortem will show significant differences between normal and cancer-derived tissues as well as between various tissue types in humans. This study also establishes critical elemental /metal profiles that may be relevant in providing correlations with the development of three major cancers. Normal human and tumor tissues of cadaverous lung, breast and liver tissues used in this study were obtained from US Biomax Company. Tissue samples were prepared using standardized digestion procedures necessary for use with the Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). This equipment was utilized to determine the concentrations and profiles of 21 elements including Ag, Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Na, Ni, Pb, Sb, Se, Sr, Tl, V, and Zn. Twelve major elements of Al, Ba, Ca, Cr, Cu, Fe, Mg, Na, Pb, Se, Sr, and Zn were found to be significantly different in term of their concentrations / profiles in normal and tumor tissues of human lung, breast and liver. These critical elements appeared to be respectively five to ten times more abundant in human lung and breast tumor than in their respective normal tissues. In contrast Ba, Cr, Cu, Fe, Zn, concentrations were shown to be lower in liver tumors than in normal liver tissues, and that Ca and Na appeared to be higher in human liver tumors than in normal liver tissues. Data analysis showed significant variations in elemental concentrations and profiles consistent with the hypothesis. It is concluded that metal / elemental homeostasis is essential for normal tissue function and that elemental variations and distributions are tissue specific as well as carcinoma specific. These results are promising and warrant further studies to confirm / exploit the possibility of manipulating elemental distribution and content as means for diagnosing / utility as therapeutic modalities in chronic human disease as well as cancer management.

Retinoids and Citral Modulated Cell Viability, Metabolic Stability, Cell Cycle Progression and Distribution in the A549 Lung Carcinoma Cell Line - Biomed 2010

Biomedical Sciences Instrumentation. 2010  |  Pubmed ID: 20467116

Lung cancer is the second leading deadly cancer in United States. In 2007, the United States reported 213,380 new lung cancer diagnoses and 160,390 deaths caused by lung cancer. Retinoic acid and retinyl esters are the oxidized and storage forms of vitamin A in the body. At low levels, they maintain many functions as hormones affecting vision, bone growth, reproduction, cellular division, and differentiation. Recent publications have found retinoid receptors to be effective therapeutic targets in some cancer cell lines and that retinoids were functional cell modulators of the RAR/RXR nuclear hormone receptors that may impact the development of lung cancer. We hypothesize that retinoic acid and retinyl esters will negatively impact the A549 lung carcinoma cell line model in vitro and that exposure to higher concentrations of retinoids will induce impairments indicative of metabolic implications seen in chronic conditions such as cancer. Citrals are specific inhibitors of retinoid metabolism and are employed to ascertain the specificity of retinoid impacts on the cell model. The aim of this study was to expose the A549 cell line model to various concentrations of retinoic acid, and Citrals (0-160 g/ml). Growth patterns of exposed cells were screened during time intervals ranging from 24-72 hours. The effects were measured through phase microscopy, cell proliferation MTT assay, FACS analysis for cell cycle parameters and western blot analyses for cyclins. Data generated from phase contrast microscopy and MTT assays showed an increased physical destruction, metabolic impairment and a decrease in the viability of A549 cell line model after 72 hours of exposure to retinoic acids and. Observations on the effects exhibited with Citrals (cis and trans vs. diethyl acetal) suggests the reversal of retinoid toxicity and a decrease in cell metabolic as well as physical destructions and positive cell proliferation. Results from FACS analysis showed modulation in the cell cycle distribution/progression upon exposure to retinoids and that Citrals did reverse these effects in the cell line model. Western blot analysis confirmed the findings obtained from testing parameters. We conclude that modulation of metabolic integrity, cell cycle distribution and cell survival through retinoids/citrals in the lung carcinoma model is promising and warrants further therapeutic investigation.

Abdominoplasty and Its Effect on Body Image, Self-esteem, and Mental Health

Annals of Plastic Surgery. Jul, 2010  |  Pubmed ID: 20467297

The impact of abdominoplasty on the quality of life of abdominoplasty patients was assessed 1- and 6-months postoperatively. Forty women aged 25 to 60 years were divided into study group (25 patients who underwent abdominoplasty) and waiting-list control group (15 patients). Three questionnaires (Body Shape Questionnaire [BSQ], Rosenberg Self-Esteem Scale [RSE/UNIFESP], and Short Form 36 Health Survey Questionnaire [SF-36]) were administered to the study group (preoperatively, 1- and 6-months postoperatively) and control group (on 2 occasions 6 months apart). A significant positive impact on body image, self-esteem, and mental health was found 1- and 6-months postoperatively. Significant differences were observed in role physical, role emotional, and vitality 1-month postoperatively. In the control group, significant differences were found for vitality. There was a significant improvement in Comparative perception of body image (6-month assessment) in the study group compared with controls. Abdominoplasty improved body image, self-esteem, and mental health.

Retinal and Ocular Toxicity in Ocular Application of Drugs and Chemicals--part I: Animal Models and Toxicity Assays

Ophthalmic Research. 2010  |  Pubmed ID: 20484950

Experimental retinal research has gained great importance due to the ophthalmic pharmacotherapy era. An increasing number of drugs are constantly released into the market for the treatment of retinal diseases. In this review, animal species, animal models and toxicity assays in retinal research are discussed.

Body Mass Index and Spontaneous Miscarriage

European Journal of Obstetrics, Gynecology, and Reproductive Biology. Aug, 2010  |  Pubmed ID: 20488611

We compared the incidence of spontaneous miscarriage in women categorised as obese, based on a Body Mass Index (BMI) >29.9 kg/m(2), with women in other BMI categories.

A Heparin Mimetic Isolated from a Marine Shrimp Suppresses Neovascularization

Journal of Thrombosis and Haemostasis : JTH. Aug, 2010  |  Pubmed ID: 20492474

 Choroidal neovascularization (CNV) is the main cause of severe visual loss in age-related macular degeneration (AMD). Heparin/heparan sulfate are known to play important roles in neovascularization due to their abilities to bind and modulate angiogenic growth factors and cytokines. Previously, we have isolated from marine shrimp a heparin-like compound with striking anti-inflammatory action and negligible anticoagulant and hemorrhagic activities.

Macular Pigment Optical Density Measured by Dual-wavelength Autofluorescence Imaging in Diabetic and Nondiabetic Patients: a Comparative Study

Investigative Ophthalmology & Visual Science. Nov, 2010  |  Pubmed ID: 20505210

To compare macular pigment optical density (MPOD) in type 2 diabetic and nondiabetic patients by using dual-wavelength autofluorescence imaging and to investigate the correlation of MPOD with glycosylated hemoglobin (HbA1C) and serum lipid levels.

Bone Marrow Stem Cell Transplantation and Coronary Artery Bypass Grafting Surgery for Chronic Ischemic Myocardiopathy

The Heart Surgery Forum. Jun, 2010  |  Pubmed ID: 20534416

We studied 12 consecutive patients with chronic ischemic myocardiopathy treated with bone marrow adult stem cell (ASC) transplantation and coronary artery bypass grafting (CABG). The aim of the study was to evaluate functional class (New York Heart Association), wall motion score index (WMSI), and ejection fraction by echocardiography and to evaluate myocardial perfusion by single-photon emission computed tomography (SPECT). Follow-up evaluations were performed at 3, 6, and 12 months. The results revealed functional class improvement until 12 months, a progressive increase in the ejection fraction of 15% to 20% in the first 6 months, and a progressive increase in the WMSI by 35% to 45% in 12 months. Evaluation of the WMSI in the stem cell and CABG areas separately revealed a similar improvement in the first 3 months and a better progression in the CABG area. SPECT images revealed perfusion improvements in ischemic areas and no difference in fibrous tissue areas. These preliminary results show the safety of the method and its reproducibility. When performed concomitantly with CABG, bone marrow ASC transplantation may improve functional class, ejection fraction, WMSI, and myocardial perfusion. This study will be completed with all patients followed up for 12 months and compared with a control group.

Retinal Nerve Fiber Layer Atrophy As Relevant Feature for Diffuse Unilateral Subacute Neuroretinitis (DUSN): Case Series

Arquivos Brasileiros De Oftalmologia. Mar-Apr, 2010  |  Pubmed ID: 20549051

To report the findings of optical coherence tomography (OCT) in three cases of diffuse unilateral subacute neuroretinitis (DUSN).

Oral Fungal Infections: an Update for the General Practitioner

Australian Dental Journal. Jun, 2010  |  Pubmed ID: 20553244

Oral candidosis is the most common fungal infection encountered in general dental practice. It manifests in a variety of clinical presentations which may mimic more sinister diseases, and can occasionally be refractory to treatment requiring the attention of an oral medicine specialist. Management of oral candidosis should always include a thorough investigation of underlying predisposing conditions, as the disease often presents when the patient is systemically compromised. This update highlights the pathogenesis, clinical presentation, and management strategies of oral Candidal lesions commonly encountered in dental practice.

Oral Mucosal Malignancy and Potentially Malignant Lesions: an Update on the Epidemiology, Risk Factors, Diagnosis and Management

Australian Dental Journal. Jun, 2010  |  Pubmed ID: 20553246

An oral examination for the assessment for malignant and potentially malignant oral mucosal lesions is routine in general dental practice. It may be uncommon for general dental practitioners to encounter oral cancer, with anecdotal reports suggesting that this occurs about once every 10 years in a busy general dental practice. However, potentially malignant oral mucosal lesions are relatively common, occurring in about 2.5% of the population. This update highlights the epidemiology, risk factors, diagnosis and management of these oral mucosal lesions.

Intravitreal Bevacizumab for Subfoveal Choroidal Neovascularization in Age-related Macular Degeneration at Twenty-four Months: the Pan-American Collaborative Retina Study

Ophthalmology. Oct, 2010  |  Pubmed ID: 20569989

To report the 24-month anatomic and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) response after primary intravitreal bevacizumab (IVB) (Avastin; Genentech Inc., San Francisco, CA) (1.25 or 2.5 mg) in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).

Does Stereochemistry Influence Transdermal Permeation of Flurbiprofen Through the Rat Skin?

Archives of Dermatological Research. Oct, 2010  |  Pubmed ID: 20582424

The possible enantioselectivity in the permeation of the chiral anti-inflammatory drug flurbiprofen across hairless rat skin was studied. The transdermal permeability of individual enantiomers from donor solution containing racemic flurbiprofen (0.1%) and pure enantiomers (0.05%) in isopropyl myristate solution was determined using side-by-side diffusion cells. The permeation profiles of enantiomers (R)- and (S)-flurbiprofen from donor solution containing racemic (RS)-flurbiprofen are comparable. When donor solution contained pure enantiomers, marked differences were observed between the permeation rates of (R)- and (S)-flurbiprofen. The steady-state flux and permeability coefficient were significantly higher for (R)-flurbiprofen in comparison with (S)-flurbiprofen (the flux ratio R/S = 2.04; p < 0.05).

Intravitreal Bevacizumab (Avastin(®)) for Diabetic Retinopathy at 24-months: The 2008 Juan Verdaguer-Planas Lecture

Current Diabetes Reviews. Sep, 2010  |  Pubmed ID: 20594160

Diabetic retinopathy (DR) remains the major threat to sight in the working age population. Diabetic macular edema (DME) is a manifestation of DR that produces loss of central vision. Proliferative diabetic retinopathy (PDR) is a major cause of visual loss in diabetic patients. In PDR, the growth of new vessels is thought to occur as a result of vascular endothelial growth factor (VEGF) release into the vitreous cavity as a response to ischemia. Furthermore, VEGF increases vessel permeability leading to deposition of proteins in the interstitium that facilitate the process of angiogenesis and macular edema. This review demonstrates multiple benefits of intravitreal bevacizumab (IVB) on DR including DME and PDR at 24 months of follow up. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse diabetic macular edema. Therefore, in the future this new therapy could replace or complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to pan-retina photocoagulation so that more selective therapy may be applied. In addition, we report a series of patients in which tractional retinal detachment developed or progressed after adjuvant preoperative IVB in severe PDR.

Clinical Factors Related to Visual Outcome in Central Serous Chorioretinopathy

Retina (Philadelphia, Pa.). Jul-Aug, 2010  |  Pubmed ID: 20616688

The purpose of this study was to describe clinical, angiographic, and tomo-graphic prognostic factors in central serous chorioretinopathy.

Effect of Carotid and Aortic Baroreceptors on Cardiopulmonary Reflex: the Role of Autonomic Function

Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas / Sociedade Brasileira De Biofísica ... [et Al.]. Jul, 2010  |  Pubmed ID: 20625658

We determined the sympathetic and parasympathetic control of heart rate (HR) and the sensitivity of the cardiopulmonary receptors after selective carotid and aortic denervation. We also investigated the participation of the autonomic nervous system in the Bezold-Jarish reflex after selective removal of aortic and carotid baroreceptors. Male Wistar rats (220-270 g) were divided into three groups: control (CG, N = 8), aortic denervation (AG, N = 5) and carotid denervation (CAG, N = 9). AG animals presented increased arterial pressure (12%) and HR (11%) compared with CG, while CAG animals presented a reduction in arterial pressure (16%) and unchanged HR compared with CG. The sequential blockade of autonomic effects by atropine and propranolol indicated a reduction in vagal function in CAG (a 50 and 62% reduction in vagal effect and tonus, respectively) while AG showed an increase of more than 100% in sympathetic control of HR. The Bezold-Jarish reflex was evaluated using serotonin, which induced increased bradycardia and hypotension in AG and CAG, suggesting that the sensitivity of the cardiopulmonary reflex is augmented after selective denervation. Atropine administration abolished the bradycardic responses induced by serotonin in all groups; however, the hypotensive response was still increased in AG. Although the responses after atropine were lower than the responses before the drug, indicating a reduction in vagal outflow after selective denervation, our data suggest that both denervation procedures are associated with an increase in sympathetic modulation of the vessels, indicating that the sensitivity of the cardiopulmonary receptors was modulated by baroreceptor fibers.

Linking the Clinical Presentation of Molar-incisor Hypomineralisation to Its Mineral Density

International Journal of Paediatric Dentistry / the British Paedodontic Society [and] the International Association of Dentistry for Children. Sep, 2010  |  Pubmed ID: 20642473

The in vitro methods used for the assessment of the severity of molar-incisor hypomineralisation (MIH) are not available for clinicians faced with questions regarding the severity in clinical cases, and the best management approach.

Diabetic Retinopathy and the Major Causes of Vision Loss in Aboriginals from Remote Western Australia

Clinical & Experimental Ophthalmology. Jul, 2010  |  Pubmed ID: 20649617

To report on diabetic retinopathy (DR) and the major causes of vision loss and blindness in Aboriginals in the Eastern Goldfields region of Western Australia between 1995 and 2007.

Antibiotic Resistance Patterns and Sequencing of Class I Integron from Uropathogenic Escherichia Coli in Lebanon

Letters in Applied Microbiology. Oct, 2010  |  Pubmed ID: 20840552

To study the prevalence and molecular basis of antimicrobial resistance in UPEC.

Venous Leg Ulcerations: a Treatment Update

Current Treatment Options in Cardiovascular Medicine. Apr, 2010  |  Pubmed ID: 20842550

OPINION STATEMENT: Selecting the appropriate treatment for venous leg ulcerations is essential for optimal wound healing and patient quality of life. Compression therapy remains the mainstay of treatment for these wounds. Compression methods should be carefully selected and tailored for compatibility with patients' daily life. Pain management should not be neglected. When response to compression therapy is limited, adjuvant therapy such as medication, débridement, or surgical procedures should be considered on an individual basis.

Incidence of Damage to the Crystalline Lens During Intravitreal Injections

Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics. Oct, 2010  |  Pubmed ID: 20874500

To report the incidence of traumatic lens injuries as a complication of intravitreal injection at 5 high-volume academic centers.

Safety and Immunogenicity Study of Multiclade HIV-1 Adenoviral Vector Vaccine Alone or As Boost Following a Multiclade HIV-1 DNA Vaccine in Africa

PloS One. 2010  |  Pubmed ID: 20877623

We conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replication-defective adenovirus type 5 (rAd5) vector expressing HIV-1 Gag and Pol from subtype B and Env from subtypes A, B and C, given alone or as boost following a DNA plasmid vaccine expressing the same HIV-1 proteins plus Nef, in 114 healthy HIV-uninfected African adults.

Bilateral Deep Brain Stimulation for Cervical Dystonia: Long-term Outcome in a Series of 10 Patients

Neurosurgery. Oct, 2010  |  Pubmed ID: 20881561

Bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) was shown to be effective in cervical dystonia refractory to medical treatment in several small short-term and 1 long-term follow-up series. Optimal stimulation parameters and their repercussions on the cost/benefit ratio still need to be established.

Meta-analysis of a Partially Hydrolysed 100%-whey Infant Formula Vs. Extensively Hydrolysed Infant Formulas in the Prevention of Atopic Dermatitis

Current Medical Research and Opinion. Nov, 2010  |  Pubmed ID: 20925453

This study presents previously unpublished point and cumulative incidence rates and relative risks (RRs) for comparing a partially hydrolysed 100% whey-based infant formula, NAN-HA * (PHF-W) to extensively hydrolysed whey- (EHF-Whey) or casein-based (EHF-Casein) infant formulas in the prevention of atopic dermatitis (AD) in infants who cannot be breastfed exclusively. It also outlines methods to convert the above-mentioned data as well as data comparing PHF-W to cows' milk formula (SF) into inputs to be applied to a pharmacoeconomic model. * NAN-HA is a registered trade name of Nestlé SA, Switzerland.

Economic Evaluation of a 100% Whey-based, Partially Hydrolysed Formula in the Prevention of Atopic Dermatitis Among French Children

Current Medical Research and Opinion. Nov, 2010  |  Pubmed ID: 20925454

A pharmacoeconomic analysis was performed to determine costs, consequences and cost effectiveness of a partially hydrolysed 100% whey-based infant formula, NAN HA, manufactured by Nestlé S.A, Switzerland (PHF-W) and branded under Nidal Excel HA in France, in the prevention of atopic dermatitis (AD) in 'at risk' children when compared to standard cows' milk formula (SF) in France.

The WD40-repeat Protein Han11 Functions As a Scaffold Protein to Control HIPK2 and MEKK1 Kinase Functions

The EMBO Journal. Nov, 2010  |  Pubmed ID: 20940704

Protein kinases are organized in hierarchical networks that are assembled and regulated by scaffold proteins. Here, we identify the evolutionary conserved WD40-repeat protein Han11 as an interactor of the kinase homeodomain-interacting protein kinase 2 (HIPK2). In vitro experiments showed the direct binding of Han11 to HIPK2, but also to the kinases DYRK1a, DYRK1b and mitogen-activated protein kinase kinase kinase 1 (MEKK1). Han11 was required to allow coupling of MEKK1 to DYRK1 and HIPK2. Knockdown experiments in Caenorhabditis elegans showed the relevance of the Han11 orthologs Swan-1 and Swan-2 for the osmotic stress response. Downregulation of Han11 in human cells lowered the threshold and amplitude of HIPK2- and MEKK1-triggered signalling events and changed the kinetics of kinase induction. Han11 knockdown changed the amplitude and time dependence of HIPK2-driven transcription in response to DNA damage and also interfered with MEKK1-triggered gene expression and stress signalling. Impaired signal transmission also occurred upon interference with stoichiometrically assembled signalling complexes by Han11 overexpression. Collectively, these experiments identify Han11 as a novel scaffold protein regulating kinase signalling by HIPK2 and MEKK1.

Regulation of Protein Kinase C Apl II by Serotonin Receptors in Aplysia

Journal of Neurochemistry. Nov, 2010  |  Pubmed ID: 20964689

Serotonin (5-hydroxytryptamine, 5HT) is the neurotransmitter that mediates dishabituation in Aplysia. Serotonin mediates this behavioral change through the reversal of synaptic depression in sensory neurons (SNs). However, the 5HT receptors present in SNs and in particular, the receptor important for activation of protein kinase C (PKC) have not been fully identified. Using a recent genome assembly of Aplysia, we identified new receptors from the 5HT(2) , 5HT(4) , and 5HT(7) families. Using RT-PCR from isolated SNs, we found that three 5HT receptors, 5HT(1Apl(a)) , 5HT(2Apl) , and 5HT(7Apl) were expressed in SNs. These receptors were cloned and expressed in a heterologous system. In this system, 5HT(2Apl) could significantly translocate PKC Apl II in response to 5HT and this was blocked by pirenperone, a 5HT(2) receptor antagonist. Surprisingly, pirenperone did not block 5HT-mediated translocation of PKC Apl II in SNs, nor 5HT-mediated reversal of depression. Expression of 5HT(1Apl(a)) in SNs or genistein, an inhibitor of tyrosine kinases inhibited both PKC translocation and reversal of depression. These results suggest a non-canonical mechanism for the translocation of PKC Apl II in SNs.

Lixivaptan, a Non-peptide Vasopressin V2 Receptor Antagonist for the Potential Oral Treatment of Hyponatremia

IDrugs : the Investigational Drugs Journal. Nov, 2010  |  Pubmed ID: 21046526

Lixivaptan (VPA-985), being developed by Biogen Idec and Cardiokine, under license from Wyeth (now part of Pfizer), is a non-peptide, selective vasopressin V2 receptor antagonist for the potential oral treatment of hyponatremia associated with heart failure. Arginine vasopressin, the native V2 receptor ligand, stimulates water reabsorption via activation of V2 receptors that are expressed in the collecting ducts of the kidney. In preclinical studies, lixivaptan displayed competitive antagonist activity at V2 receptors in vitro, and increased urine volume and decreased urine osmolality in rats and dogs. The therapeutic benefits of lixivaptan are being evaluated in patients with conditions that are associated with water excess and hyponatremia. Phase II clinical trials in patients with congestive heart failure, liver cirrhosis with ascites or syndrome of inappropriate antidiuretic hormone have demonstrated that, unlike traditional diuretics, lixivaptan increases water clearance without affecting renal sodium excretion or activating the neurohormonal system. Administration of lixivaptan in combination with the diuretic furosemide has been tested in rats as well as in trials in healthy volunteers, in which the two agents were well tolerated. Ongoing phase III trials will determine the role of lixivaptan in the management of hyponatremia, especially when associated with heart failure.

[Sarcoma Botryoides of the Uterine Cervix]

La Tunisie Médicale. Nov, 2010  |  Pubmed ID: 21049428

Quetiapine Overdose

The Australian and New Zealand Journal of Psychiatry. Dec, 2010  |  Pubmed ID: 21070111

Female Workers and in Vivo Lung Monitoring: a Simple Model for Morphological Dependence of Counting Efficiency Curves

Physics in Medicine and Biology. Dec, 2010  |  Pubmed ID: 21081821

This paper addresses the question of the morphological dependence of counting efficiency curves for in vivo lung monitoring of workers, with a particular focus on the case of female workers for whom different chest girth and cup size are considered. A library of 24 female torsos, with chest girth varying from 85 to 120 and cup size from A to F, was constructed using mesh and NURBS formats. The anatomical realism and usefulness of these models for simulating in vivo counting measurements are illustrated and simulations are reported for a typical 4-germanium (Ge) counting system. A simple analytic formula describing the relation between efficiency curves obtained for each female phantom is given. This formula uses the mass attenuation coefficient for adipose tissue and two parameters which are dependant on lung volume and breast weight. The model is tested against Monte Carlo simulated data, experimental data obtained with the Livermore phantom and published data. The model correctly describes the efficiency curve and, since the parameters depend on the counting geometry, it is shown how to estimate them from experimental measurements.

[Ocular Pharmacology in the Treatment of Vitreous, Retina and Choroid Diseases]

Arquivos Brasileiros De Oftalmologia. May-Jun, 2010  |  Pubmed ID: 20730292

Retinal diseases are frequently causes of impaired visual acuity and blindness. Recent progress in ocular pharmacology leads to the development of new promising drugs and better functional outcomes. Drug delivery and local management of diseases affecting the choroid and retina should enable better anatomical and functional outcomes. An overview of ocular pharmacology, emerging drug technologies and drug delivery is provided. Some relevant clinical features are discussed.

Sclerochorioretinal Abnormalities in Hypercholesterolemic Rabbits Treated with Rosiglitazone

Ophthalmic Surgery, Lasers & Imaging : the Official Journal of the International Society for Imaging in the Eye. Sep-Oct, 2010  |  Pubmed ID: 20795574

To evaluate early retinal, choroidal, and scleral abnormalities induced by a hypercholesterolemic diet and the prevention of these abnormalities after oral administration of rosiglitazone in rabbits.

Thermochemical Ablation in an Ex-vivo Porcine Liver Model Using Acetic Acid and Sodium Hydroxide: Proof of Concept

Journal of Vascular and Interventional Radiology : JVIR. Oct, 2010  |  Pubmed ID: 20801679

To establish proof of concept in tissue, using the exothermic neutralization reaction of acetic acid and sodium hydroxide in ex vivo porcine liver and to conduct an initial probe into the relationships of volume and concentration of reagents to temperatures and the areas affected.

Methylnaltrexone in the Treatment Of Opioid-Induced Constipation in Cancer Patients Receiving Palliative Care: Willingness-to-Pay and Cost-Benefit Analysis

Journal of Pain and Symptom Management. Sep, 2010  |  Pubmed ID: 20832981

CONTEXT: When laxative regimens have failed, methylnaltrexone may be indicated for the relief of opioid-induced constipation (OIC) in patients with advanced illness receiving palliative care. OBJECTIVES: A cost-benefit analysis (CBA), based on a willingness-to-pay (WTP) approach, was performed to determine if methylnaltrexone should be added to the formulary list of drugs being reimbursed by third-party payers in Canada for the treatment of cancer patients in palliative care suffering from OIC. METHODS: The WTP study had two components: a decision board explaining treatment options (Component A) and a questionnaire to measure individual WTP using a bidding game approach (Component B). Component A had two options: Option 1 (laxatives only) and Option 2 (laxatives+methylnaltrexone injection). Only participants choosing Option 2 were invited to complete Component B. The results of the WTP survey were then incorporated into a CBA. Within a hypothetical cohort, additional monthly premiums that individuals were willing to pay for methylnaltrexone were compared with the monthly costs to the insurer for providing methylnaltrexone to all patients who would potentially be using it. RESULTS: Four hundred one Canadians, of age 18 years and older, were surveyed and yielded a WTP in additional monthly insurance premiums of Canadian dollar, CAD$8.65 (95% confidence interval: CAD$6.17-CAD$11.13). The CBA resulted in additional CAD$89,307 with a cost of CAD$139,840 and benefits of CAD$229,147. A set of 10,000 Monte Carlo simulations resulted in average CBA savings of CAD$145,011 with a 99.86% probability of dominance. CONCLUSION: The present CBA provides pharmacoeconomic evidence for the adoption of methylnaltrexone for treating OIC in terminally ill cancer patients.

Investigating 22q11.2 Deletion and Other Chromosomal Aberrations in Fetuses with Heart Defects Detected by Prenatal Echocardiography

Pediatric Cardiology. Nov, 2010  |  Pubmed ID: 20848279

Congenital heart disease (CHD) is the most common birth defect and the leading cause of mortality in the first year of life. In fetuses with a heart defect, chromosomal abnormalities are very frequent. Besides aneuploidy, 22q11.2 deletion is one of the most recognizable chromosomal abnormalities causing CHD. The frequency of this abnormality varies in nonselected populations. This study aimed to investigate the incidence of the 22q11.2 deletion and other chromosomal alterations in a Brazilian sample of fetuses with structural cardiac anomalies detected by fetal echocardiography. In a prospective study, 68 fetuses with a heart defect were evaluated. Prenatal detection of cardiac abnormalities led to identification of aneuploidy or structural chromosomal anomaly in 35.3% of these cases. None of the fetuses with apparently normal karyotypes had a 22q11.2 deletion. The heart defects most frequently associated with chromosomal abnormalities were atrioventricular septal defect (AVSD), ventricular septal defect (VSD), and tetralogy of Fallot. Autosomal trisomies 18 and 21 were the most common chromosomal abnormalities. The study results support the strong association of chromosome alterations and cardiac malformation, especially in AVSD and VSD, for which a chromosome investigation is indicated. In fetuses with an isolated conotruncal cardiopathy, fluorescence in situ hybridization (FISH) to investigate a 22q11.2 deletion is not indicated.

Early Activation of the Interleukin-23-17 Axis in a Murine Model of Oropharyngeal Candidiasis

Molecular Oral Microbiology. Oct, 2010  |  Pubmed ID: 20883223

Candida albicans is an oral commensal yeast that causes oropharyngeal candidiasis (OPC) in immunocompromised individuals. The immunological pathways involved in OPC have been revisited after the interleukin-17 (IL-17) pathway was implicated in fungal immunity. We studied immediate (<24 h) and adaptive (3-6 day) IL-12 and IL-23-17 pathway activation in naive p40(-/-) mice, which lack IL-12 and IL-23 and develop severe, chronic OPC upon oral inoculation with C. albicans. Macrophages from p40(-/-) mice were less efficient than C57BL/6J controls at killing C. albicans in vitro but very low numbers in the oral mucosae of infected C57BL/6J mice suggest that they are not critical in vivo, at least in this strain. Migration of macrophages to regional lymph nodes of infected p40(-/-) mice was impaired; however, dendritic cell migration was not affected. Recombinant IL-12 therapy provided only temporary relief from OPC, suggesting that IL-23 is required for full protection. In C57BL/6J mice, but not p40(-/-) mice, messenger RNAs encoding IL-23p19 and IL-17 were induced in the oral mucosa within 24 h of infection (6 ± 0.6 and 12 ± 2.7-fold). By day 6 of infection in C57BL/6J mice, IL-17A messenger RNA level had increased 5.1 ± 1.8 and 83 ± 21-fold in regional lymph nodes and oral tissues respectively. Ablation of p40 was associated with delayed or abrogated induction of IL-17A pathway targets (monocyte chemoattractant protein-1, IL-6 and macrophage inflammatory protein-2), and a lack of organized recruitment of neutrophils to the infected oral mucosa. Overall our data show that the IL-23-17A axis is activated early in the oral mucosae of immunologically naive mice with OPC.

Moderate Exercise Prevents Impaired Ca2+ Handling in Heart of CO-exposed Rat: Implication for Sensitivity to Ischemia-reperfusion

American Journal of Physiology. Heart and Circulatory Physiology. Dec, 2010  |  Pubmed ID: 20889839

Sustained urban carbon monoxide (CO) exposure exacerbates heart vulnerability to ischemia-reperfusion via deleterious effects on the antioxidant status and Ca(2+) homeostasis of cardiomyocytes. The aim of this work was to evaluate whether moderate exercise training prevents these effects. Wistar rats were randomly assigned to a control group and to CO groups, living during 4 wk in simulated urban CO pollution (30-100 parts/million, 12 h/day) with (CO-Ex) or sedentary without exercise (CO-Sed). The exercise procedure began 4 wk before CO exposure and was maintained twice a week in standard filtered air during CO exposure. On one set of rats, myocardial ischemia (30 min) and reperfusion (120 min) were performed on isolated perfused rat hearts. On another set of rats, myocardial antioxidant status and Ca(2+) handling were evaluated following environmental exposure. As a result, exercise training prevented CO-induced myocardial phenotypical changes. Indeed, exercise induced myocardial antioxidant status recovery in CO-exposed rats, which is accompanied by a normalization of sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a expression and then of Ca(2+) handling. Importantly, in CO-exposed rats, the normalization of cardiomyocyte phenotype with moderate exercise was associated with a restored sensitivity of the myocardium to ischemia-reperfusion. Indeed, CO-Ex rats presented a lower infarct size and a significant decrease of reperfusion arrhythmias compared with their sedentary counterparts. To conclude, moderate exercise, by preventing CO-induced Ca(2+) handling and myocardial antioxidant status alterations, reduces heart vulnerability to ischemia-reperfusion.

Creation and Use of Adjustable 3D Phantoms: Application for the Lung Monitoring of Female Workers

Health Physics. Nov, 2010  |  Pubmed ID: 20938235

In vivo counting measurements, used for the monitoring of workers with internal contamination risks, are based on the use of calibration physical phantoms. However, such phantoms do not exist for female subjects. Computational calibration using numerical representations, Mesh and non-uniform rational basis spline (NURBS) geometries, was thus considered. The study presented here is focused on the creation of different female thoracic phantoms with various breast sizes and chest girths. These 3D models are used to estimate the radiation attenuation with morphology and the resulting variation of the calibration coefficient of a typical 4-germanium in vivo counting system. A basic Mesh female thoracic phantom was created from the International Commission on Radiological Protection Adult Female Reference Computational Phantom. Using this basic phantom, different chest girths (85, 90, 100, 110, and 120) and cup sizes (A to F) were created representing the most common thoracic female morphologies, as recommended by the available and relevant literature. Variation of breast tissue composition and internal organ volumes with morphology were also considered. As a result, 34 thoracic female phantoms were created combining different cup sizes and chest girths. For the 85 chest girth, at very low energies (15 keV), a relative counting efficiency variation of about 85% was observed between the A and E cups. As a result of this study, breast size dependent calibration coefficients, between 15 keV and 1.4 MeV, were obtained and tabulated for a typical lung counting germanium system.

Reactive Molecular Dynamics with Material-specific Coarse-grained Potentials: Growth of Polystyrene Chains from Styrene Monomers

The Journal of Physical Chemistry. B. Nov, 2010  |  Pubmed ID: 20939547

We have developed a reactive molecular dynamics (RMD) scheme to simulate irreversible polymerization of realistic polymer systems in a coarse-grained resolution. We have studied the chain propagation of styrene to polystyrene. For monodisperse polystyrene samples, we reproduce the results of equilibrium MD simulations: density, end-to-end distance, radius of gyration, and different geometrical distribution functions. The RMD simulations on polydisperse systems should be considered as case studies intended to understand the influence of different tuning parameters of the RMD approach on calculated polymer quantities. The parameters for the irreversible polymerization include the number and position of the initiator units (I*) as well as capture radii r(I) (r(P)) defining the geometrical conditions for chain initiation (propagation) and a characteristic delay time τ(r) separating two reactive MD time steps. As a function of the r(I) (r(P)) and τ(r), it is possible to model polymerization processes both in the limit of almost unrelaxed and fully relaxed samples. The strong influence of the spatial localization of the I* on the polymer size distribution is discussed in detail. The RMD results are used to formulate optimized computational conditions for the simulation of irreversible polymerizations, to explain observed trends in the polydispersity index, and to suggest experiments that might lead to an unexpected polymer size distribution.

Modeling Weight Loss and Chlorogenic Acids Content in Coffee During Roasting

Journal of Agricultural and Food Chemistry. Nov, 2010  |  Pubmed ID: 21049932

Roasting is a key step in the production of a high-quality coffee. Roasting degree is directly related to coffee chemical composition and may be determined objectively by weight loss after roasting. Chlorogenic acids (CGA) are thermally labile phenolic compounds that play an important role in the final cup quality and health benefits of coffee. Considering the interest in finding a reliable method to predict weight loss and CGA content in coffee, models have been developed to estimate these parameters during roasting. Weight loss was successfully modeled (r = 0.99) independent of the instant temperature. CGA degradation followed first-order Arrhenius-compliant kinetic models with good predictability (r = 0.98), especially for light to moderately dark samples. In both cases distinct models for Coffea arabica and Coffea canephora were calculated, because of differences in chemical composition and cell wall structure between these species. The proposed models may become important predictive tools in the coffee industry.

Technique Sensitivity in Bonding to Enamel and Dentin

Compendium of Continuing Education in Dentistry (Jamesburg, N.J. : 1995). Sep, 2010  |  Pubmed ID: 21053440

Bonding to enamel and dentin has been among the most significant advancements in dentistry in the last five decades; extensive research and product development have resulted in more adhesive options. However, bonding to enamel and dentin still proves to be challenging, and selecting the correct product for a clinical application can be confusing. An incorrect choice can lead to insufficient bond strength. Day-to-day clinical factors, such as the presence of enamel, superficial dentin, or carious dentin, as well as contamination by saliva, blood, or bleaching agents, can cause bonding agents to be technique sensitive-they may fail prematurely if steps are not followed meticulously. This article attempts to simplify the selection process for enamel and dentinal bonding and summarize clinically relevant bonding information that will help produce consistently successful results.

The Impact of Preexisting Myocardial Remodeling on Ventricular Function Early After Tetralogy of Fallot Repair

Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. Sep, 2010  |  Pubmed ID: 20650609

Twenty-three patients (median age 23 months) who underwent Fallot's tetralogy repair were investigated prospectively to detect a possible association between histopathologic myocardial remodeling and echocardiographic findings of systolic or diastolic ventricular dysfunction.

Autonomic Reactivity to Cold Pressor Test in Prehypertensive and Hypertensive Medical Students

Indian Journal of Physiology and Pharmacology. Jul-Sep, 2011  |  Pubmed ID: 22471232

Autonomic reactivity to stress has been hypothesized to be a marker for subsequent neurogenic hypertension. Medical training is highly stressful particularly for those who are beginning their medical education. The present study was undertaken to study the autonomic reactivity to cold pressor test in prehypertensive and hypertensive undergraduate medical students. One hundred and seventeen undergraduate medical students between 17-21 years of age got examined for blood pressure and stress level. Twelve Hypertensives and eight prehypertensives selected from the above subjects and twenty normotensives underwent cold pressure test (CPT) to assess autonomic reactivity to laboratory induced stress. 10.25% of the subjects were found to be hypertensive and 6.83% pre hypertensive. On the stress scale 53% had mild stress, 7% showed moderate stress while none had stress as a major problem. There was no correlation between BP and stress score. On CPT, BP increased significantly in all the three groups (hypertensive, prehypertensive and normotensive) but came back to basal levels within 5 minutes indicating normal autonomic response. Rise of BP was higher in hypertensive group as compared to normotensive group. The rise of diastolic and mean BP during CPT was significantly higher in subjects having family history of hypertension. Forty percent of normotensive subjects had more than 20 mm Hg rise in systolic BP on CPT. Adolescents must be routinely screened to detect asymptomatic hypertension. The CPT may identify individuals with an occult physiological abnormality that predisposes them to hypertension in their later life.

Accelerated Wound Healing Phenotype in Interleukin 12/23 Deficient Mice

Journal of Inflammation (London, England). 2011  |  Pubmed ID: 22185520

ABSTRACT:

Eight Primary Malignancies: Case Report and Review of Literature

Hematology/oncology and Stem Cell Therapy. 2011  |  Pubmed ID: 22198190

The incidence of multiple primary malignancies has increased over the past years secondary to the long-term survival of cancer patients due to improvements in the early detection and adequate treatment of cancer. We present a patient with eight primary malignant tumors and review the relevant literature. Our patient was a 59-year-old female with Crohn disease with an otherwise non-contributory medical history. Risk factors for multiple primary tumors were not detected in our patient. At a follow-up of 108 months from the time of diagnosis of the first malignancy, our patient was still alive. Similar long-term survival has been reported in the literature. Due to the realistic potential for long-term survival, we recommend aggressive treatment of these patients.

Spontaneous Rupture of a Giant Hepatic Hemangioma. Sequential Treatment with Preoperative Transcatheter Arterial Embolization and Conservative Hepatectomy

Il Giornale Di Chirurgia. Nov-Dec, 2011  |  Pubmed ID: 22217374

Hemangioma is the most common benign tumor of the liver and it is often asymptomatic. Spontaneous rupture of liver hemangiomas is a rare but potentially lethal complication. Emergent hepatic resection has been the treatment of choice but carries high operative morbidity and mortality. Recently, preoperative transcatheter arterial embolization (TAE) has been used successfully for the management of bleeding ruptured liver tumors and non-operative treatment of symptomatic giant liver hemangiomas. We report a case of spontaneous rupture of a giant hepatic hemangioma that presented with thoracic and abdominal pain and shock due to hemoperitoneum. Once proper diagnosis was made the patient was successfully managed by TAE, followed by conservative hepatic resection.

Development of Multiplex Real-time PCR for the Rapid Detection of Five Bacterial Causes of Community Acquired Pneumonia

Tropical Biomedicine. Dec, 2011  |  Pubmed ID: 22433883

Establishing a microbial diagnosis for patients with community-acquired pneumonia (CAP) is still challenging and is often achieved in only 30-50% of cases. Polymerase chain reaction (PCR) has been shown to be more sensitive than conventional microbiological methods and it could help to increase the microbial yield for CAP patients. This study was designed to develop, optimize and evaluate multiplex real-time PCR as a method for rapid differential detection of five bacterial causes of CAP namely Streptococcus pneumoniae, Burkholderia pseudomallei and atypical bacterial pathogens, Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila. Duplex and triplex real-time PCR assays were developed using five sets of primers and probes that were designed based on an appropriate specific gene for each of the above CAP pathogens. The performance of primers for each organism was tested using SYBR Green melt curve analysis following monoplex realtime PCR amplification. Monoplex real-time PCR assays were also used to optimize each primers-probe set before combining them in multiplex assays. Two multiplex real-time PCR assays were then optimized; duplex assay for the differential detection of S. pneumoniae and B. pseudomallei, and triplex assay for the atypical bacterial pathogens. Both duplex and triplex real-time PCR assays were tested for specificity by using DNA extracted from 26 related microorganisms and sensitivity by running serial dilutions of positive control DNAs. The developed multiplex real-time PCR assays shall be used later for directly identifying CAP causative agents in clinical samples.

Construction of an Extended Library of Adult Male 3D Models: Rationale and Results

Physics in Medicine and Biology. Dec, 2011  |  Pubmed ID: 22086354

In order to best cover the possible extent of heights and weights of male adults the construction of 25 whole body 3D models has been undertaken. Such a library is thought to be useful to specify the uncertainties and relevance of dosimetry calculations carried out with models representing individuals of average body heights and weights. Representative 3D models of Caucasian body types are selected in a commercial database according to their height and weight, and 3D models of the skeleton and internal organs are designed using another commercial dataset. A review of the literature enabled one to fix volume or mass target values for the skeleton, soft organs, skin and fat content of the selected individuals. The composition of the remainder tissue is fixed so that the weight of the voxel models equals the weight of the selected individuals. After mesh and NURBS modelling, volume adjustment of the selected body shapes and additional voxel-based work, 25 voxel models with 109 identified organs or tissue are obtained. Radiation transport calculations are carried out with some of the developed models to illustrate potential uses. The following points are discussed throughout this paper: justification of the fixed or obtained models’ features regarding available and relevant literature data; workflow and strategy for major modelling steps; advantages and drawbacks of the obtained library as compared with other works. The construction hypotheses are explained and justified in detail since future calculation results obtained with this library will depend on them.

Optimal Time Needed for Withdrawal of Mechanical Ventilation in Patients with Chronic Obstructive Pulmonary Disease

The Israel Medical Association Journal : IMAJ. Oct, 2011  |  Pubmed ID: 22097230

Exacerbations of chronic obstructive pulmonary disease (COPD) are a major problem worldwide and are usually the main indication for mechanical ventilation (MV), especially in the intensive care unit (ICU). The rate of weaning failure is also high and prolonged MV leads to complications of intubation. The goal is to wean these patients as soon as possible.

Influence of Maternal Glycemia on Intrauterine Fetal Adiposity Distribution After a Normal Oral Glucose Tolerance Test at 28 Weeks Gestation

Experimental Diabetes Research. 2011  |  Pubmed ID: 22110474

To examine the relationship between maternal glucose levels and intrauterine fetal adiposity distribution in women with a normal oral glucose tolerance test (OGTT) at 28 weeks gestation.

What Models of Maternity Care Do Pregnant Women in Ireland Want?

Irish Medical Journal. Jun, 2011  |  Pubmed ID: 22111395

The introduction of new models of care in the Irish maternity services has been recommended by both advocacy groups and strategic reports. Yet there is a dearth of information about what models of care pregnant women want. We surveyed women in early pregnancy who were attending a large Dublin maternity hospital. Demographic and clinical details were recorded from the hospital chart. Of the 501 women, 351 (70%) (352 (70.3%) of women wanted shared antenatal care between their family doctor and either a hospital doctor or midwife. 228 (45.5%) preferred to have their baby delivered in a doctor-led unit, while 215 (42.9%) preferred a midwifery-led unit. Of those 215 (42.9%), 118 (55%) met criteria for suitability. There was minimal demand (1.6%) for home births. Choice was influenced by whether the woman was attending for private care or not. Safety is the most important factor for women when choosing the type of maternity care they want. Pregnant women want a wide range of choices when it comes to models of maternity care. Their choice is strongly influenced by safety considerations, and will be determined in part by risk assessment.

Simultaneous Confocal Scanning Laser Ophthalmoscopy Combined with High-resolution Spectral-domain Optical Coherence Tomography: a Review

Journal of Ophthalmology. 2011  |  Pubmed ID: 22132313

We aimed to evaluate technical aspects and the clinical relevance of a simultaneous confocal scanning laser ophthalmoscope and a high-speed, high-resolution, spectral-domain optical coherence tomography (SDOCT) device for retinal imaging. The principle of confocal scanning laser imaging provides a high resolution of retinal and choroidal vasculature with low light exposure. Enhanced contrast, details, and image sharpness are generated using confocality. The real-time SDOCT provides a new level of accuracy for assessment of the angiographic and morphological correlation. The combined system allows for simultaneous recordings of topographic and tomographic images with accurate correlation between them. Also it can provide simultaneous multimodal imaging of retinal pathologies, such as fluorescein and indocyanine green angiographies, infrared and blue reflectance (red-free) images, fundus autofluorescence images, and OCT scans (Spectralis HRA + OCT; Heidelberg Engineering, Heidelberg, Germany). The combination of various macular diagnostic tools can lead to a better understanding and improved knowledge of macular diseases.

Surgical Management of Impacted Teeth Using Three-dimensional Computed Tomography

The Journal of Craniofacial Surgery. Nov, 2011  |  Pubmed ID: 22134273

The surgical removal of impacted, supernumerary, or ectopic teeth is a routine procedure to the dental surgeon. Because any and all surgical interventions involve anatomic considerations that predispose the patient to a high risk of incidents or complications, it is absolutely necessary to precisely determine the location of the enclosed teeth, to better plan the procedure. Even though the conventional radiographic techniques are commonly used to detect the presence of such teeth, they can present deficiencies. In those situations, additional examinations can be requested. In this article, we are reporting the case of a 12-year-old patient, whose third superior molars appeared in a very atypical position. We chose to request a computed tomography and three-dimensional manipulation of the obtained images. This article, as its main goal, highlighted the importance of computed tomography and of three-dimensional reconstructions as a tool to precisely determine the location of enclosed teeth, thus allowing for a better planning of the surgery and a safer surgical intervention.

The Rates of Protein Synthesis and Degradation Account for the Differential Response of Neurons to Spaced and Massed Training Protocols

PLoS Computational Biology. Dec, 2011  |  Pubmed ID: 22219722

The sensory-motor neuron synapse of Aplysia is an excellent model system for investigating the biochemical changes underlying memory formation. In this system, training that is separated by rest periods (spaced training) leads to persistent changes in synaptic strength that depend on biochemical pathways that are different from those that occur when the training lacks rest periods (massed training). Recently, we have shown that in isolated sensory neurons, applications of serotonin, the neurotransmitter implicated in inducing these synaptic changes during memory formation, lead to desensitization of the PKC Apl II response, in a manner that depends on the method of application (spaced versus massed). Here, we develop a mathematical model of this response in order to gain insight into how neurons sense these different training protocols. The model was developed incrementally, and each component was experimentally validated, leading to two novel findings: First, the increased desensitization due to PKA-mediated heterologous desensitization is coupled to a faster recovery than the homologous desensitization that occurs in the absence of PKA activity. Second, the model suggests that increased spacing leads to greater desensitization due to the short half-life of a hypothetical protein, whose production prevents homologous desensitization. Thus, we predict that the effects of differential spacing are largely driven by the rates of production and degradation of proteins. This prediction suggests a powerful mechanism by which information about time is incorporated into neuronal processing.

Inhibitory Properties of Coffea Canephora Extract Against Oral Bacteria and Its Effect on Demineralisation of Deciduous Teeth

Archives of Oral Biology. Jun, 2011  |  Pubmed ID: 21185010

The antibacterial activity of Coffea canephora extract was evaluated in vitro against Streptococcus mutans and Streptococcus sobrinus. The viability of planktonic cells was analysed by susceptibility tests (MIC and MBC) and time-kill assays. The effect of the extract on dental demineralisation was also investigated.

Perspective on Fluid and Solid Dynamics in Different Pars Plana Vitrectomy Systems

American Journal of Ophthalmology. Mar, 2011  |  Pubmed ID: 21251644

To summarize current concepts and recent data from the literature about different vitrectomy machines and small-gauge systems based on physical laws.

Adolescents with and Without Gestational Cocaine Exposure: Longitudinal Analysis of Inhibitory Control, Memory and Receptive Language

Neurotoxicology and Teratology. Jan-Feb, 2011  |  Pubmed ID: 21256423

Preclinical studies of gestational cocaine exposure (GCE) show evidence of changes in brain function at the anatomical, physiological, and behavioral levels, to include effects on developing dopaminergic systems. In contrast, human studies have produced less consistent results, with most showing small effects or no effects on developmental outcomes. Important changes in brain structure and function occur through adolescence, therefore it is possible that prenatal cocaine exposure has latent effects on neurocognitive (NC) outcome that do not manifest until adolescence or young adulthood. We examined NC function using a set of 5 tasks designed to tap 4 different systems: inhibitory control, working memory, receptive language, and incidental memory. For each NC task, data were collected longitudinally at ages 12, 14.5 and 17 years and examined using generalized estimating equations. One hundred and nine children completed at least two of the three evaluations. Covariates included in the final model were assessment number, gender, participant age at first assessment, caregiver depression, and two composites from the Home Observation for Measurement of the Environment (HOME), Environmental Stimulation and Parental Nurturance. We found no cocaine effects on inhibitory control, working memory, or receptive language (p=0.18). GCE effects were observed on incidental face memory task (p=0.055), and GCE by assessment number interaction effects were seen on the incidental word memory task (p=0.031). Participant performance on inhibitory control, working memory, and receptive language tasks improved over time. HOME Environmental Stimulation composite was associated with better receptive language functioning. With a larger sample size smaller differences between groups may have been detected. This report shows no evidence of latent effects of GCE on inhibitory control, working memory, or receptive language. GCE effects were observed on the incidental face memory task, and GCE by assessment number interaction effects was seen on the incidental word memory task.

Impaired Glucose Tolerance Plus Hyperlipidaemia Induced by Diet Promotes Retina Microaneurysms in New Zealand Rabbits

International Journal of Experimental Pathology. Feb, 2011  |  Pubmed ID: 21272105

With the increasing prevalence of diabetes mellitus and metabolic syndrome worldwide, experimental models are required to better understand the pathophysiology and therapeutic approaches to preserve pancreatic beta cells, attenuate atherosclerosis and protect target organs. The aims of this study were to develop an experimental model of impaired glucose tolerance combined with hypercholesterolaemia induced by diet and assess metabolic alterations and target organ lesions. New Zealand male rabbits were fed high-fat/high-sucrose (10/40%) and cholesterol-enriched diet for 24 weeks, when they were sacrificed. Biochemistry, fundus photographs with fluorescein angiography and pathological analyses were performed. Cholesterol-fed and normal animals of same age were compared. Results: The animals with diet-induced impaired glucose tolerance combined with hypercholesterolaemia gained weight, increased blood glucose, total cholesterol, LDL-C and triglycerides and decreased HDL-C (P < 0.05 vs. baseline). Fructosamine levels and the homeostasis model assessment of insulin resistance (HOMA-IR) index were increased, while there was a reduction in the HOMA-β (P < 0.05 for all vs. baseline). Histomorphologic findings of this model were aortic atherosclerosis, hepatic steatofibrosis and glomerular macrophage infiltration. Early clinical features of diabetic retinopathy with hyperfluorescent dots consistent with presence of retina microaneurysms were seen since week 12, progressing up to the end of the experiment (P < 0.0005 vs. baseline and 12 weeks). Our model reproduced several metabolic characteristics of human diabetes mellitus and promoted early signs of retinopathy. This non-expensive model is suitable for studying mechanistic pathways and allowing novel strategic approaches.

Occult Breast Malignancy Masquerading As Acute Hepatic Failure

Gastroenterology & Hepatology. Jan, 2011  |  Pubmed ID: 21346857

The Influence of Maternal Body Composition on Birth Weight

European Journal of Obstetrics, Gynecology, and Reproductive Biology. Jul, 2011  |  Pubmed ID: 21353373

To identify the maternal body composition parameters that independently influence birth weight.

Endophthalmitis After Pars Plana Vitrectomy: Results of the Pan American Collaborative Retina Study Group

Retina (Philadelphia, Pa.). Apr, 2011  |  Pubmed ID: 21394065

To determine the incidence of endophthalmitis after 20-, 23-, and 25-gauge pars plana vitrectomies (PPVs).

Red Cell Distribution Width and Mortality in Predominantly African-American Population with Decompensated Heart Failure

Journal of Cardiac Failure. Apr, 2011  |  Pubmed ID: 21440866

Red-cell distribution width (RDW) has been identified as a novel prognostic marker in heart failure patients. However, evidence is limited for its predictive value in the setting of patients hospitalized with decompensated heart failure (DHF) and no data are available for African Americans (AA).

Demographic Determinants of Risk, Colon Distribution and Density Scores of Diverticular Disease

World Journal of Gastroenterology : WJG. Feb, 2011  |  Pubmed ID: 21448352

To investigate associations between ethnicity, age and sex and the risk, colon distribution and density scores of diverticular disease (DD).

Predictors of Airway Hyperresponsiveness Differ Between Old and Young Patients with Asthma

Chest. Jun, 2011  |  Pubmed ID: 21454398

Age-related increases in morbidity and mortality due to asthma may be due to changes in pathophysiology as patients with asthma get older. There is limited knowledge about the effects of age on the predictors of airway hyperresponsiveness (AHR), a key feature of asthma. The aim of this study was to determine if the pathophysiologic predictors of AHR, including inflammation, ventilation heterogeneity, and airway closure, differed between young and old patients with asthma.

Comparative Reliability Analyses of Zirconium Oxide and Lithium Disilicate Restorations in Vitro and in Vivo

Journal of the American Dental Association (1939). Apr, 2011  |  Pubmed ID: 21454834

The authors analyzed the in vitro and in vivo performance of lithium disilicate glass-ceramic (LDGC) restorations and yttria-stabilized tetragonal zirconia polycrystalline (Y-TZP) (that is, zirconium oxide) restorations with regard to reliability, clinical performance and abrasion resistance.

Molecular Characterization and Resistance Profile of Salmonella Enteritidis PT4 and PT9 Strains Isolated in Brazil

Journal of Medical Microbiology. Jul, 2011  |  Pubmed ID: 21459909

A total of 41 Salmonella Enteritidis strains, including phago-types (PTs) PT4 and PT9, were characterized by antimicrobial resistance profiles and PFGE. Of these strains, 34 were isolated from patients and foods, and 7 were of poultry origin. All strains were susceptible to ampicillin, chloramphenicol, cefotaxime, ciprofloxacin and trimethoprim/sulfamethoxazole, and 41.5 % (n = 17) were resistant to nalidixic acid. PFGE analysis using XbaI and SpeI restriction enzymes resulted in X1S1 as the prevalent pattern, which was present in 48.8 % (n = 20) of epidemic strains and in one strain isolated from discarded hatching eggs. Distinct patterns were found for the other strains isolated from poultry (X3S1, X8S8, X11S12, X11S13, X16S1 and X13S15). The S. Enteritidis PT9 strains associated with outbreaks of salmonellosis were highly similar (≥0.90), suggesting clonality. The PFGE genotypes were related to the PTs, and it was possible to differentiate strains isolated from patients with salmonellosis from other strains of non-epidemic origin. The PFGE results suggested that the S. Enteritidis strains of poultry origin were a possible source of human salmonellosis during the study period.

A Comparison of Maternal and Paternal Body Mass Index in Early Pregnancy

The Australian & New Zealand Journal of Obstetrics & Gynaecology. Apr, 2011  |  Pubmed ID: 21466517

 To determine the body mass index (BMI) and the body composition of fathers-to-be and to compare the findings with those of mothers-to-be during early pregnancy.

Comparison of a Single Intravitreal Injection of Bevacizumab Versus Triamcinolone Acetonide As Primary Treatment for Diffuse Diabetic Macular Oedema

Acta Ophthalmologica. Apr, 2011  |  Pubmed ID: 21470386

A Prospective, Randomized Evaluation of a Novel Everolimus-eluting Coronary Stent: the PLATINUM (a Prospective, Randomized, Multicenter Trial to Assess an Everolimus-Eluting Coronary Stent System [PROMUS Element] for the Treatment of Up to Two De Novo Coronary Artery Lesions) Trial

Journal of the American College of Cardiology. Apr, 2011  |  Pubmed ID: 21470815

We sought to evaluate the clinical outcomes with a novel platinum chromium everolimus-eluting stent (PtCr-EES) compared with a predicate cobalt chromium everolimus-eluting stent (CoCr-EES) in patients undergoing percutaneous coronary intervention (PCI).

Reduced BACE1 Activity Enhances Clearance of Myelin Debris and Regeneration of Axons in the Injured Peripheral Nervous System

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Apr, 2011  |  Pubmed ID: 21490216

β-Site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is an aspartyl protease best known for its role in generating the amyloid-β peptides that are present in plaques of Alzheimer's disease. BACE1 has been an attractive target for drug development. In cultured embryonic neurons, BACE1-cleaved N-terminal APP is further processed to generate a fragment that can trigger axonal degeneration, suggesting a vital role for BACE1 in axonal health. In addition, BACE1 cleaves neuregulin 1 type III, a protein critical for myelination of peripheral axons by Schwann cells during development. Here, we asked whether axonal degeneration or axonal regeneration in adult nerves might be affected by inhibition or elimination of BACE1. We report that BACE1 knock-out and wild-type nerves degenerated at a similar rate after axotomy and to a similar extent in the experimental neuropathies produced by administration of paclitaxel and acrylamide. These data indicate N-APP is not the sole culprit in axonal degeneration in adult nerves. Unexpectedly, however, we observed that BACE1 knock-out mice had markedly enhanced clearance of axonal and myelin debris from degenerated fibers, accelerated axonal regeneration, and earlier reinnervation of neuromuscular junctions, compared with littermate controls. These observations were reproduced in part by pharmacological inhibition of BACE1. These data suggest BACE1 inhibition as a therapeutic approach to accelerate regeneration and recovery after peripheral nerve damage.

Photonic Crystal Fiber for Efficient Raman Scattering of CdTe Quantum Dots in Aqueous Solution

ACS Nano. May, 2011  |  Pubmed ID: 21517094

A novel hollow-core photonic crystal fiber platform was used for the first time to observe clear vibrational modes of the CdTe core, CdS(0.7)Te(0.3) interface, and carboxylate-metal complexes in dilute aqueous CdTe quantum dot (QD) solutions. These modes demonstrate the presence of crystalline cores, defects, and surface passivation responsible for photoluminescent efficiency and stability. In addition, 3-mercaptopropionic acid (MPA)-capped QDs show higher crystallinity and stability than those capped with thioglycolic acid (TGA) and 1-thioglycerol (TG). This detailed, nondestructive characterization was carried out using Raman spectroscopy for solutions with QD concentration of 2 mg/mL, which is similar to their concentration during synthesis process. This platform can be extended to the in situ studies of any colloidal nanoparticles and aqueous solutions of relevant biological samples using Raman spectroscopy.

Impact of Supra-physiologic Retinoids on Ovalbumin-sensitized F344 Lung Tissue and Reversal of Related Pathology by Citral - Biomed 2011

Biomedical Sciences Instrumentation. 2011  |  Pubmed ID: 21525620

The role of retinoids (All Trans Retinoic Acid; ATRA, and Retinyl Palmitate; RP) in the development of lung hypervitaminosis A pathology is not well understood or established in the literature. As well, the role of Citral (inhibitor of retinoid function) in the reversal of lung pathology is also not ascertained under an in vivo setting. Therefore, it is hypothesized that ovalbumin exposure will sensitize lung tissues to supra-physiologic levels of retinoids leading to tissue pathology and that Citral 1 and 2 will reverse or ameliorate the related pathological damage to lung tissues. Even though ovalbumin and retinoids have been previously applied through intra-tracheal route in cancer prevention and immunological research, the objective of this pilot study was to evaluate techniques, establish functional dosing and generate preliminary data before further experimentation. This IACUC approved in vivo study consist of twenty one (n = 21) Fischer 344 rats (200 to 400g) which were randomly assigned to controls and two ovalbumin-sensitized treatment groups (low; 0.15 mg/kg and high; 0.30 mg/kg, all sensitized by intra-peritoneal injection at day 1) and were also dosed at day 7 with 40 and 80 mg/kg each of ATRA or RP as well as 20 and 50 mg/kg each of Citrals 1 or 2 individually or in combination to represent low and high for all four chemicals, which were administered by intra-peritoneal injection. Citral is a non-toxic chemical that exists in two forms (diethyl; C1 or cis-trans dimethyl; C2). Positive and negative controls for each treatment were also included in the study. Animals were housed in rat cages at the JSU Research Animal Core Facilities and were placed on a 12:12 light–dark cycle. A standard rodent diet and water access were provided adlibidum. Rat weights were recorded on Day 1 and 21, all animals were sacrificed on day 21 and lung tissues were processed for histopathology. Slides were prepared and were digitized for comparison of tissues pathology. Results showed that even though C1 and C2 were not toxic individually, their combination at high dosing was lethal. As well, the combination of high dosing of RP and C1 was also lethal. Exposure of ovalbumin-sensitized rats to ATRA showed various levels of lung tissue damage that was not ameliorated by Citrals. RP exposure caused various levels of tissue damage that was not reversed by either C1 or C2. Taken together, the study showed that there are variable pathologic responses from the interaction of ovalbumin, Citrals and retinoids and those Citrals failed in reversing tissue pathologies. These findings warrants further investigation as to the actual role of these interactions in relation to chronic lung disease and the possibility of reversing retinoid-mediated pathologies in the Fisher rat model.

Assessing the Survival of Mrc-5 and A549 Cell Lines Upon Exposure to Ascorbic Acid and Sodium Ascorbate - Biomed 2011

Biomedical Sciences Instrumentation. 2011  |  Pubmed ID: 21525621

Lung cancer is among the highly prevalent and deadly cancers in the United States and worldwide. Cells that are cancerous exhibit higher rates of glycolysis as compared to normal cells. In an attempt to exploit this uniquely enhanced glucose-dependent ATP generation phenomenon, the authors hypothesize that exposure of cancer cells to normal organic metabolites that are capable of inhibiting glycolysis would have a negative impact on survival by altering growth and viability characteristics vastly through decline in ATP build up essentially leading to collapse in energy supply; normal lung cells will not demonstrate such changes. The human lung fibroblast cell line MRC-5 and the cancerous human lung alveolar epithelial cell line A549 were utilized in this study as in vitro models of normal and cancerous lung cell lines respectively. Using standard methods, both cell lines were maintained in culture and exposed to ascorbic acid and sodium ascorbate reagents at concentration levels ranging from 31.3-2,000 µg/ml. Cell survival measurements using MTT andT4 Cellometric assays monitored with phase-contrast photo-imaging were carried out in quadruplicates. Results indicate that exposure characteristics to these metabolites followed concentration-dependent cell mortality/survival curves by the cancerous versus normal cell lines respectively. Ascorbic acid and sodium ascorbate showed statistically significant (p<0.05) differential negative effects on the cancerous A549 cell line in comparison to unexposed controls as well as to effects measured with the normal lung MRC-5 cell line; this is highly indicative of a promising therapeutic potential.

Combined Topical and Systemic Clonazepam Therapy for the Management of Burning Mouth Syndrome: a Retrospective Pilot Study

Journal of Orofacial Pain. 2011  |  Pubmed ID: 21528119

To evaluate retrospectively the efficacy of administering an anticonvulsant medication, clonazepam, by dissolving tablets slowly orally before swallowing, for the management of burning mouth syndrome (BMS).

Incidence and Predictors of Ventricular Arrhythmias After ST-segment Elevation Myocardial Infarction

The American Journal of Emergency Medicine. May, 2011  |  Pubmed ID: 21570242

BACKGROUND: Sustained ventricular arrhythmias (VA) complicate 7% to 20% of acute myocardial infarctions. We hypothesized that primary angioplasty (percutaneous coronary intervention [PCI]) and contemporary medical treatment will result in a lower incidence of VA and shorten the time frame of their occurrence. Thus, an electrocardiographic monitoring period of 24 hours should be sufficient to detect more than 95% of all malignant VA. METHODS: We continuously monitored all patients with ST-segment elevation myocardial infarction (STEMI) for 48 hours. RESULTS: Of the 510 patients who underwent PCI for STEMI, 24 (4.7%) developed sustained VA. Sixty percent of sustained VA occurred during the first 24 hours; and 92%, during the first 48 hours. In univariate analysis, heart rate greater than 100 beats per minute, Thrombolysis in Myocardial Infarction flow grade less than 3, elevated creatinine (≥1 mg/dL), elevated C-reactive protein (≥0.8 mg/dL), higher white blood cell count (≥12 × 10(3)/μL), use of diuretics, and lower hematocrit (≤39%) were associated with an increased risk of VA. Symptom-onset-to-balloon time of 4 hours or more in patients with postprocedural Thrombolysis in Myocardial Infarction 3 flow, treatment with β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins were associated with a reduced risk of VA. After multivariate adjustment, independent predictors of sustained VA included total white blood cell count of 12 × 10(3)/μL or more, hematocrit of 39% or less, and lack of β-blocker medication. CONCLUSIONS: In this study, we could demonstrate that primary PCI results in a lower incidence of VA compared with data from the literature but did not shorten the time frame of VA occurrence. Thus, an electrocardiographic monitoring period for VA of 48 hours should be performed in patients with STEMI.

[Vacuum-assisted Therapy for Various Wound Types Including Diabetic Foot Ulcer]

Harefuah. Mar, 2011  |  Pubmed ID: 21574351

Vacuum is a noninvasive system that creates a localized controlled negative pressure environment. In this study, vacuum was provided by the V.A.C. Therapy system, which promotes wound healing by delayed primary or secondary intention through creating a moist wound environment, preparing the wound bed for closure, reducing edema, and promoting formation and perfusion of granulation tissue. Vacuum-assisted closure therapy is indicated for use in all care settings and for a variety of wound types including diabetic foot ulcers.

Intravitreal Bevacizumab (Avastin) for Diabetic Retinopathy: The 2010 GLADAOF Lecture

Journal of Ophthalmology. 2011  |  Pubmed ID: 21584260

This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB) on diabetic retinopathy (DR) including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD), and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy.

A Component of the Xanthomonadaceae Type IV Secretion System Combines a VirB7 Motif with a N0 Domain Found in Outer Membrane Transport Proteins

PLoS Pathogens. May, 2011  |  Pubmed ID: 21589901

Type IV secretion systems (T4SS) are used by Gram-negative bacteria to translocate protein and DNA substrates across the cell envelope and into target cells. Translocation across the outer membrane is achieved via a ringed tetradecameric outer membrane complex made up of a small VirB7 lipoprotein (normally 30 to 45 residues in the mature form) and the C-terminal domains of the VirB9 and VirB10 subunits. Several species from the genera of Xanthomonas phytopathogens possess an uncharacterized type IV secretion system with some distinguishing features, one of which is an unusually large VirB7 subunit (118 residues in the mature form). Here, we report the NMR and 1.0 Å X-ray structures of the VirB7 subunit from Xanthomonas citri subsp. citri (VirB7(XAC2622)) and its interaction with VirB9. NMR solution studies show that residues 27-41 of the disordered flexible N-terminal region of VirB7(XAC2622) interact specifically with the VirB9 C-terminal domain, resulting in a significant reduction in the conformational freedom of both regions. VirB7(XAC2622) has a unique C-terminal domain whose topology is strikingly similar to that of N0 domains found in proteins from different systems involved in transport across the bacterial outer membrane. We show that VirB7(XAC2622) oligomerizes through interactions involving conserved residues in the N0 domain and residues 42-49 within the flexible N-terminal region and that these homotropic interactions can persist in the presence of heterotropic interactions with VirB9. Finally, we propose that VirB7(XAC2622) oligomerization is compatible with the core complex structure in a manner such that the N0 domains form an extra layer on the perimeter of the tetradecameric ring.

The Risk of Caesarean Section in Obese Women Analysed by Parity

European Journal of Obstetrics, Gynecology, and Reproductive Biology. Sep, 2011  |  Pubmed ID: 21596472

This study looked at the association between caesarean section (CS) and Body Mass Index (BMI) in primigravidas compared with multigravidas.

Usefulness of Various Inflammatory Markers to Differentiate Pulmonary Edema from Pneumonia

The Israel Medical Association Journal : IMAJ. Apr, 2011  |  Pubmed ID: 21598811

Community-acquired pneumonia requiring hospitalization is a severe illness with high mortality, especially if the appropriate treatment is delayed. Sometimes diagnosis is difficult due to an equivocal clinical picture or chest film, or to accompanying diseases that mask or simulate pneumonia.

Triazoloquinazolines As a Novel Class of Phosphodiesterase 10A (PDE10A) Inhibitors

Bioorganic & Medicinal Chemistry Letters. Jun, 2011  |  Pubmed ID: 21602043

Novel triazoloquinazolines have been found as phosphodiesterase 10A (PDE10A) inhibitors. Structure-activity studies improved the initial micromolar potency which was found in the lead compound by a 100-fold identifying 5-(1H-benzoimidazol-2-ylmethylsulfanyl)-2-methyl-[1,2,4]triazolo[1,5-c]quinazoline, 42 (PDE10A IC(50)=12 nM) as the most potent compound from the series. Two X-ray structures revealed novel binding modes to the catalytic site of the PDE10A enzyme.

Effect of Simultaneous Consumption of Milk and Coffee on Chlorogenic Acids' Bioavailability in Humans

Journal of Agricultural and Food Chemistry. Jul, 2011  |  Pubmed ID: 21627318

Different studies have shown that milk may interact with polyphenols and affect their bioavailability in humans. The present study investigated the effect of the simultaneous consumption of coffee and milk on the urinary excretion of chlorogenic acids (CGA) and metabolites. Subjects were submitted to consumption of water, instant coffee (609 mmol of CGA) dissolved in water, and instant coffee dissolved in whole milk. Urine was collected for 24 h after consumption of each treatment for analysis of CGA and metabolites by HPLC/LC-MS. The amount of CGA and metabolites recovered after consumption of combined coffee-milk (40% ± 27%) was consistently lower in all subjects compared to that of coffee alone (68% ± 20%). Concluding, the simultaneous consumption of milk and coffee may impair the bioavailability of coffee CGA in humans.

Toxicological Considerations for Intravitreal Drugs

Expert Opinion on Drug Metabolism & Toxicology. Aug, 2011  |  Pubmed ID: 21627546

INTRODUCTION: Intravitreal injections are a very common procedure and are the most effective route of drug delivery to the retina. There are currently several drugs available and even more are in development; therefore, safety is a very important concern. AREAS COVERED: The toxicological considerations of the most common drugs used for intravitreal pharmacotherapy such as anti-VEGFs, corticosteroids and antibiotics. Emerging agents such as anti-TNFs, VEGF-trap and kinase inhibitors are also discussed. An assessment of the efficacy and safety issues of the most relevant drugs including bevacizumab, ranibizumab and triamcinolone is presented. EXPERT OPINION: The toxicology and safety profiles are available for several drugs that are either in use or will be available for intravitreal injections. Retinal pharmacotherapy is very effective for different retinal diseases; however safety is a very important issue when intravitreal injections are applied and the possibility of retinal toxicity should always be kept in mind. Bevacizumab and ranibizumab are effective for the therapy of wet-age-related macular degeneration and macular edema, while triamcinolone remains an alternative agent to treat secondary macular edema. It is important, as some of these drugs will be used for extended periods of time, that their long-term toxicological effects are better understood.

Development of a New CBR-based Platform for Human Contamination Emergency Situations

Radiation Protection Dosimetry. Mar, 2011  |  Pubmed ID: 21115445

In the case of a radiological emergency situation, involving accidental human exposure, it is necessary to establish as soon as possible a dosimetry evaluation. In most cases, this evaluation is based on numerical representations and models of the victims. Unfortunately, personalised and realistic human representations are often unavailable for the exposed subjects. Hence, existing models like the 'Reference Man' representative of the average male individual are used. However, the accuracy of the treatment depends on the similarity of the phantom to the victim. The EquiVox platform (Research of Equivalent Voxel phantom) developed in this work uses the case-based reasoning principles to retrieve, from a set of existing phantoms, the most adapted one to represent the victim. This paper introduces the EquiVox platform and gives the example of in vivo lung monitoring optimisation to prove its efficiency in choosing the right model. It also presents the artificial neural network tools being developed to adapt the model to the victim.

Experimental Investigation of Needles, Syringes and Techniques for Intravitreal Injections

Clinical & Experimental Ophthalmology. Apr, 2011  |  Pubmed ID: 20973898

To assess the techniques and materials used in intravitreal injections.

Examples of Mesh and NURBS Modelling for in Vivo Lung Counting Studies

Radiation Protection Dosimetry. Mar, 2011  |  Pubmed ID: 21030397

Realistic calibration coefficients for in vivo counting installations are assessed using voxel phantoms and Monte Carlo calculations. However, voxel phantoms construction is time consuming and their flexibility extremely limited. This paper involves Mesh and non-uniform rational B-splines graphical formats, of greater flexibility, to optimise the calibration of in vivo counting installations. Two studies validating the use of such phantoms and involving geometry deformation and modelling were carried out to study the morphologic effect on lung counting efficiency. The created 3D models fitted with the reference ones, with volumetric differences of <5 %. Moreover, it was found that counting efficiency varies with the inverse of lungs' volume and that the latter primes when compared with chest wall thickness. Finally, a series of different thoracic female phantoms of various cup sizes, chest girths and internal organs' volumes were created starting from the International Commission on Radiological Protection (ICRP) adult female reference computational phantom to give correction factors for the lung monitoring of female workers.

A Baeyer-Villiger Oxidation Specifically Catalyzed by Human Flavin-containing Monooxygenase 5

Drug Metabolism and Disposition: the Biological Fate of Chemicals. Jan, 2011  |  Pubmed ID: 20947616

10-((4-Hydroxypiperidin-1-yl)methyl)chromeno[4,3,2-de]phthalazin-3(2H)-one (E7016), an inhibitor of poly(ADP-ribose) polymerase, is being developed for anticancer therapy. One of the major metabolites identified in preclinical animal studies was the product of an apparent oxidation and ring opening of the 4-hydroxypiperidine. In vitro, this oxidized metabolite could not be generated by incubating E7016 with animal or human liver microsomes. Further studies revealed the formation of this unique metabolite in hepatocytes. In a NAD(P)(+)-dependent manner, this metabolite was also generated by liver S9 fractions and recombinant human flavin-containing monooxygenase (FMO) 5 that was fortified with liver cytosol fractions. In animal and human liver S9, this metabolic pathway could be inhibited by 4-methylpyrazole, bis-p-nitrophenylphosphate (BNPP), or a brief heat treatment at 50°C. Based on these results, the overall metabolic pathway was believed to involve a two-step oxidation process: dehydrogenation of the secondary alcohol in liver cytosol followed by an FMO5-mediated Baeyer-Villiger oxidation in liver microsomes. The two oxidation steps were coupled via regeneration of NAD(P)(+) and NAD(P)H. To further confirm this mechanism, the proposed ketone intermediate was independently synthesized. In an NAD(P)H-dependent manner, the synthetic ketone intermediate was metabolized to the same ring-opened metabolite in animal and human liver microsomes. This metabolic reaction was also inhibited by BNPP or a brief heat treatment at 50°C. Methimazole, the substrate/inhibitor of FMO1 and FMO3, did not inhibit this reaction. The specificity of FMO5 toward catalyzing this Baeyer-Villiger oxidation was further demonstrated by incubating the synthetic ketone intermediate in recombinant enzymes.

Novel Vitreous Modulators for Pharmacologic Vitreolysis in the Treatment of Diabetic Retinopathy

Current Pharmaceutical Biotechnology. Mar, 2011  |  Pubmed ID: 20939794

Vitreous constitutes about 80% of the volume of the human eye. It is an extended extracellular matrix that is composed of collagen, hyaluronan, and other extracellular matrix molecules, but mostly water. In both health as well as disease, especially diabetic retinopathy (DR), special attention should be drawn to the posterior vitreous cortex and its relation to the retinal surface. The important role of vitreous in the pathogenesis of proliferative DR has already been demonstrated by several experimental and clinical studies. Thus, vitreo-retinal separation by pharmacologic vitreolysis and/or removal by surgical means are appropriate approaches to interrupt the pathogenic contribution of vitreous and prevent progression of diabetic retinopathy to more advanced stages. This review describes various aspects of the molecular morphology and structural anatomy of vitreous and the vitreo-retinal interface, as well as the role of vitreous in the pathophysiology of DR. Lastly, this treatise provides a critical analysis of novel vitreous modulators for pharmacologic vitreolysis in the treatment of DR. Microplasmin is currently the most promising approach to treat vitreoretinal traction by pharmacologic vitreolysis.

Calciphylaxis in the Current Era: Emerging 'ironic' Features?

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. Jan, 2011  |  Pubmed ID: 20627865

Calcific uraemic arteriolopathy (CUA), previously known as calciphylaxis, is a condition of microvascular calcification and thrombosis with resultant tissue necrosis. Due to the rarity of this disease, our understanding of its pathogenesis remains speculative. Iron has emerged as a potential pathogenic contributor to the development of CUA, but investigation into this link is lacking. The purpose of our study was to explore the clinical characteristics of patients diagnosed with CUA at our institution to allow for comparison to available literature. In addition, we wanted to pursue the possibility of iron being a pathogenic contributor to CUA development. We hypothesized that iron would have to be present in areas of microvascular calcification in order to play a contributing pathogenic role and, therefore, wished to establish whether iron deposition was present within available diagnostic CUA skin biopsy specimens.

Maternal Leptin and Body Composition in the First Trimester of Pregnancy

Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. Apr, 2011  |  Pubmed ID: 20528571

Leptin is produced mainly by adipocytes. Levels are increased in women with obesity and during pregnancy. Increased levels are also associated with pregnancy complications such as, pre-eclampsia and gestational diabetes mellitus.

Overcorrecting the Neuroenhancement Discussion

Addiction (Abingdon, England). Jun, 2011  |  Pubmed ID: 21564378

Body Mass Index and Blood Pressure Measurement During Pregnancy

Hypertension in Pregnancy : Official Journal of the International Society for the Study of Hypertension in Pregnancy. 2011  |  Pubmed ID: 20726743

The accurate measurement of blood pressure requires the use of a large cuff in subjects with a high mid-arm circumference (MAC). This prospective study examined the need for a large cuff during pregnancy and its correlation with maternal obesity.

Discriminant Value of Serum HBV DNA Levels As Predictors of Liver Fibrosis in Chronic Hepatitis B

Journal of Viral Hepatitis. Jul, 2011  |  Pubmed ID: 21692936

Current guidelines recommend antiviral therapy in chronic hepatitis B (HBV) patients with significant histological disease. We aimed to compare histological fibrosis (METAVIR, ≥F2) in patients with HBV DNA ≥20,000 IU/mL vs. ≥2000 IU/mL and identify predictors of fibrosis. We performed prospective liver biopsies on 203 HBeAg-negative patients in four groups: Group I (n = 55): HBV DNA ≥20,000 IU/mL and persistently elevated alanine aminotransferase (ALT) levels (PEALT; >40 U/L); Group II (n = 34): HBV DNA ≥20,000 IU/mL and persistently normal ALT (PNALT); Group III (n = 40): HBV DNA <20,000 IU/mL and PEALT; and Group IV (n = 74): HBV DNA <20,000 IU/mL, and PNALT. We reanalysed all groups in relation to updated cut-off for treatable viremia (2000 IU/mL). Genotype D was detected in 86% of patients. Hepatic fibrosis ≥F2 was detected in 72.7%, 52.9%, 57.5% and 18.9% in Groups I-IV, respectively (P < 0.0001). Except in Group II with a trend for lower ≥F2 fibrosis (P = 0.067), there was no significant difference by using HBV DNA cut-off 20,000 vs. 2000 IU/mL. Multivariate logistic regression analysis identified study Group IV (OR, 0.0276; CI: 0.088-0.868; P = 0.0276) and milder (A0-1) necroinflammatory grade (OR, 0.135; CI: 0.063-0.287; P < 0.0001) as independent predictors of ≥F2 fibrosis. The specificity, positive and negative predictive values for PEALT in detection of ≥F2 fibrosis for viremia ≥2000 IU/mL (80%, 69% and 65%, respectively) or ≥20,000 IU/mL (86%, 73% and 63%, respectively) were similar, with a marginal gain in sensitivity (51% vs. 42%, respectively). Significant fibrosis is prevalent in a large proportion of HBeAg-negative patients with high viremia and persistently normal ALT. Lower HBV DNA cut-offs could be adopted with marginal gains in fibrosis detection and without loss of diagnostic accuracy.

Diverse Protective Roles of the Actin Cytoskeleton During Oxidative Stress

Cytoskeleton (Hoboken, N.J.). Jun, 2011  |  Pubmed ID: 21634027

Actin oxidation is known to result in changes in cytoskeleton organization and dynamics. Actin oxidation is clinically relevant since it occurs in the erythrocytes of sickle cell patients and may be the direct cause of the lack of morphological plasticity observed in irreversibly sickled red blood cells (ISCs). During episodes of crisis, ISCs accumulate C284-C373 intramolecularly disulfide bonded actin, which reduces actin filament dynamics. Actin cysteines 284 and 373 (285 and 374 in yeast) are conserved, suggesting that they play an important functional role. We have been investigating the physiological roles of these cysteines using the model eukaryote Saccharomyces cerevisiae in response to oxidative stress load. During acute oxidative stress, all of the F-actin in wild-type cells collapses into a few puncta that we call oxidation-induced actin bodies (OABs). In contrast, during acute oxidative stress the actin cytoskeleton in Cys-to-Ala actin mutants remains polarized longer, OABs are slower to form, and the cells recover more slowly than wild-type cells, suggesting that the OABs play a protective role. Live cell imaging revealed that OABs are large, immobile structures that contain actin-binding proteins and that can form by the fusion of actin cortical patches. We propose that actin's C285 and C374 may help to protect the cell from oxidative stress arising from normal oxidative metabolism and contribute to the cell's general adaptive response to oxidative stress.

Ultrasonography Compared to Magnetic Resonance Imaging in Thyroid-associated Graves' Ophthalmopathy

Arquivos Brasileiros De Endocrinologia E Metabologia. Apr, 2011  |  Pubmed ID: 21655866

To compare ultrasonography (US) to magnetic resonance imaging (MRI) and the clinical activity score (CAS) in Graves' ophthalmopathy.

Efficacy of Tissue Autofluorescence Imaging (velscope) in the Visualization of Oral Mucosal Lesions

Head & Neck. Aug, 2011  |  Pubmed ID: 21818819

BACKGROUND: Technology that highlights potentially malignant oral lesions in a highly sensitive and specific manner will aid clinicians in early diagnosis of these conditions. This study assessed the efficacy of direct tissue autofluorescence imaging Visually Enhanced Lesion Scope (VELScope) in the detection of oral mucosal lesions. METHODS: One hundred twelve patients referred with a potentially malignant oral mucosal lesion were examined under routine incandescent light, and then with VELScope, noting loss of autofluorescence and presence of blanching. Incisional biopsies were performed to provide definitive histopathological diagnoses. RESULTS: VELScope enhanced the visibility of 41 lesions and helped uncover 5 clinically undetected lesions. VELScope examination alone showed a sensitivity of 30% and a specificity of 63%. Its accuracy at identifying dysplasia was 55%. CONCLUSION: VELScope examination cannot provide a definitive diagnosis regarding the presence of epithelial dysplasia. Loss of autofluorescence is not useful in diagnosing epithelial dysplasia in its own right without relevant clinical interpretation. © 2011 Wiley Periodicals, Inc. Head Neck, 2011.

The Effect of Airway Remodelling on Airway Hyper-responsiveness in Asthma

Respiratory Medicine. Dec, 2011  |  Pubmed ID: 21820298

The mechanisms of airway hyper-responsiveness are only partially understood and the contribution of airway remodelling is unknown. Airway remodelling can be assessed by measuring airway distensibility, which is reduced in asthma, even when lung function is normal. We hypothesised that airway remodelling contributes to airway hyper-responsiveness in asthma, independent of steroid-responsive airway inflammation.

Comparison in Maternal Body Composition Between Caucasian Irish and Indian Women

Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. Aug, 2011  |  Pubmed ID: 21823843

The use of body mass index (BMI) for the diagnosis of obesity has limitations, especially when comparing ethnic groups with different body proportions. The aim of this prospective study was to compare maternal body composition in early pregnancy between Caucasian Irish and Indian women. A total of 81 Indian women and 81 Irish Caucasian women were matched for age, parity and BMI. Maternal weight and height were measured, and body composition analysed using bioelectrical impedance. The Irish women were taller and weighed more than the Indian women (p<0.001). At any given BMI, the Indian women had a higher total body fat percentage, visceral fat level and high fat percentage than the Irish women (p=0.024, 0.001 and 0.001, respectively). Our findings suggest that lower BMI cut-offs should be used for screening for gestational diabetes mellitus in Indian women attending our antenatal services.

Are Prescription Stimulants "smart Pills"? The Epidemiology and Cognitive Neuroscience of Prescription Stimulant Use by Normal Healthy Individuals

Psychological Bulletin. Sep, 2011  |  Pubmed ID: 21859174

Use of prescription stimulants by normal healthy individuals to enhance cognition is said to be on the rise. Who is using these medications for cognitive enhancement, and how prevalent is this practice? Do prescription stimulants in fact enhance cognition for normal healthy people? We review the epidemiological and cognitive neuroscience literatures in search of answers to these questions. Epidemiological issues addressed include the prevalence of nonmedical stimulant use, user demographics, methods by which users obtain prescription stimulants, and motivations for use. Cognitive neuroscience issues addressed include the effects of prescription stimulants on learning and executive function, as well as the task and individual variables associated with these effects. Little is known about the prevalence of prescription stimulant use for cognitive enhancement outside of student populations. Among college students, estimates of use vary widely but, taken together, suggest that the practice is commonplace. The cognitive effects of stimulants on normal healthy people cannot yet be characterized definitively, despite the volume of research that has been carried out on these issues. Published evidence suggests that declarative memory can be improved by stimulants, with some evidence consistent with enhanced consolidation of memories. Effects on the executive functions of working memory and cognitive control are less reliable but have been found for at least some individuals on some tasks. In closing, we enumerate the many outstanding questions that remain to be addressed by future research and also identify obstacles facing this research.

Multi-intervention Management of Calciphylaxis: a Report of 7 Cases

American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. Dec, 2011  |  Pubmed ID: 21872378

Calcific uremic arteriolopathy (calciphylaxis) is a devastating but rare complication seen predominantly in dialysis patients that often is fatal. Because of the rarity of the disease and the multifactorial nature of its cause, no clinical trials have been conducted to date to determine the best therapy for the condition. We report a case series of 7 patients at a single institution in whom a systematic multi-interventional treatment strategy was implemented, consisting of trigger-agent cessation (calcium-based phosphate binders, alphacalcidol, and warfarin), wound management, and antibiotic therapy, supplemented by intensified hemodialysis (4 hours daily for 7 days followed by 5-6 times weekly), intravenous sodium thiosulfate (12.5-25 g intravenously 3 times a week), and attempted oxygen therapy (given through a face mask or hyperbaric chamber as tolerated by patient circumstance). Treatments selected were based on literature review, consensus discussion, and attempts to address the physiologic disturbances that underlie the condition. All 7 patients identified with biopsy-proven calcific uremic arteriolopathy were treated with this regimen in 2007-2010, with 6 of 7 showing complete recovery. We suggest that consistent implementation of a multi-interventional approach may alter the course of this devastating disease. Further studies are needed to confirm and extend these findings.

Obesity is a Determinant of Asthma Control Independent of Inflammation and Lung Mechanics

Chest. Sep, 2011  |  Pubmed ID: 21415135

It is unclear why obesity is associated with worse asthma control. We hypothesized that (1) obesity affects asthma control independent of spirometry, airway inflammation, and airway hyperresponsiveness (AHR) and (2) residual symptoms after resolution of inflammation are due to obesity-related changes in lung mechanics.

Polycystic Ovary Syndrome and the Peripheral Blood White Cell Count

Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2011  |  Pubmed ID: 21417649

This retrospective cross-sectional study examined if the white cell count (WCC) is increased in women with polycystic ovary syndrome (PCOS) and if so, is it due to PCOS or to the associated obesity? Body mass index (BMI) was calculated and body composition was measured using bioelectrical impedance analysis. Of the 113 women studied, 36 had PCOS and 77 did not. The mean WCC was higher in the PCOS group compared with the non-PCOS group (8.9 × 10(9)/l vs 7.4 × 10(9)/l p = 0.002). This increase was due to a higher neutrophil count (5.6 × 10(9)/l vs 4.3 × 10(9)/l; p = 0.003). There was a leucocytosis (WCC >11 × 10(9)/l) present in 19% of the PCOS group compared with 1% in the non-PCOS group (p < 0.001). The neutrophil count was abnormally high (>7.7 × 10(9)/l) in 14% of the PCOS group compared with 4% in the non-PCOS group (p < 0.001). On regression analysis, however, the only independent variable which explained both the increased WCC and the increased neutrophil count was PCOS. We found that PCOS is associated with an increased WCC due to increased neutrophils, which supports the evidence that PCOS is associated with low-grade inflammation. The increase appears to be due to the underlying PCOS, and not to the increased adiposity associated with PCOS.

Influence of Trypanocidal Therapy on the Haematology of Vervet Monkeys Experimentally Infected with Trypanosoma Brucei Rhodesiense

Acta Tropica. Jul, 2011  |  Pubmed ID: 21420376

The aim of this study was to characterise the sequential haematological changes in vervet monkeys infected with Trypanosoma brucei rhodesiense and subsequently treated with sub-curative diminazene aceturate (DA) and curative melarsoprol (MelB) trypanocidal drugs. Fourteen vervet monkeys, on a serial timed-kill pathogenesis study, were infected intravenously with 10(4) trypanosomes of a stabilate T. b. rhodesiense KETRI 2537. They were treated with DA at 28 days post infection (dpi) and with MelB following relapse of infection at 140 dpi. Blood samples were obtained from the monkeys weekly, and haematology conducted using a haematological analyser. All the monkeys developed a disease associated with macrocytic hypochromic anaemia characterised by a reduction in erythrocytes (RBC), haemoglobin (HB), haematocrit (HCT), mean cell volume (MCV), platelet count (PLT), and an increase in the red cell distribution width (RDW) and mean platelet volume (MPV). The clinical disease was characteristic of human African trypanosomiasis (HAT) with a pre-patent period of 3 days. Treatment with DA cleared trypanosomes from both the blood and cerebrospinal fluid (CSF). The parasites relapsed first in the CSF and later in the blood. This treatment normalised the RBC, HCT, HB, PLT, MCV, and MPV achieving the pre-infection values within two weeks while RDW took up to 6 weeks to attain pre-infection levels after treatment. Most of the parameters were later characterised by fluctuations, and declined at one to two weeks before relapse of trypanosomes in the haemolymphatic circulation. Following MelB treatment at 140 dpi, most values recovered within two weeks and stabilised at pre-infection levels, during the 223 days post treatment monitoring period. It is concluded that DA and MelB treatments cause similar normalising changes in the haematological profiles of monkeys infected with T. b. rhodesiense, indicating the efficacy of the drugs. The infection related changes in haematology parameters, further characterise the vervet monkey as an optimal induced animal model of HAT. Serial monitoring of these parameters can be used as an adjunct in the diagnosis and prognosis of the disease outcome in the vervet monkey model.

Moxonidine Improves Cardiac Structure and Performance in SHR Through Inhibition of Cytokines, P38 MAPK and Akt

British Journal of Pharmacology. Oct, 2011  |  Pubmed ID: 21426316

Regression of left ventricular hypertrophy by moxonidine, a centrally acting sympatholytic imidazoline compound, results from a sustained reduction of DNA synthesis and transient stimulation of DNA fragmentation. Because apoptosis of cardiomyocytes may lead to contractile dysfunction, we investigated in spontaneously hypertensive rats (SHR), time- and dose-dependent effects of in vivo moxonidine treatment on cardiac structure and function as well as on the inflammatory process and signalling proteins involved in cardiac cell survival/death.

[Bilateral Chronic and Granulomatous Total Uveitis Following Cutaneous Leishmaniasis]

Médecine Et Maladies Infectieuses. Jun, 2011  |  Pubmed ID: 21493026

Peripartum Hysterectomy in the First Decade of the 21st Century

Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. May, 2011  |  Pubmed ID: 21534754

We reviewed the role of peripartum hysterectomy (PH) in the first decade of the 21st century. The study was confined to women who delivered a baby weighing 500 g or more between 2000 and 2009, and who required a hysterectomy within 72 h of delivery for obstetric reasons. Individual case records were reviewed. There were 19 cases of PH in 78,961 deliveries giving an incidence of 1 in 4,156 (0.02%). Of the 19 cases, 95% were delivered by caesarean section and 89% had one or more prior sections. The indications were placental bed pathology (79%), uterine atony (16%) and uterine trauma (5%). Of the 19 hysterectomies, 16 (84%) were total and a gynaecological oncologist was involved in nine (56%) of these cases. There were no maternal or fetal deaths, but a mother required an average blood transfusion of 10 units. The overall rate of PH was remarkably low compared with other studies but it is likely to increase in the future because of the strong association between increasing caesarean section rates and placental bed pathology. The potential involvement of the cervix and other pelvic structures by placental pathology means that PH in the future will be more challenging, and the hysterectomy will need to be total rather than subtotal.

Taking Organelles Apart, Putting Them Back Together and Creating New Ones: Lessons from the Endoplasmic Reticulum

Progress in Histochemistry and Cytochemistry. Jun, 2011  |  Pubmed ID: 21536318

The endoplasmic reticulum (ER) is a highly dynamic organelle. It is composed of four subcompartments including nuclear envelope (NE), rough ER (rER), smooth ER (sER) and transitional ER (tER). The subcompartments are interconnected, can fragment and dissociate and are able to reassemble again. They coordinate with cell function by way of protein regulators in the surrounding cytosol. The activity of the many associated molecular machines of the ER as well as the fluid nature of the limiting membrane of the ER contribute extensively to the dynamics of the ER. This review examines the properties of the ER that permit its isolation and purification and the physiological conditions that permit reconstitution both in vitro and in vivo in normal and in disease conditions.

Cytokines in Neovascular Age-related Macular Degeneration: Fundamentals of Targeted Combination Therapy

The British Journal of Ophthalmology. Dec, 2011  |  Pubmed ID: 21546514

The neovascular form of age-related macular degeneration (AMD), called wet-AMD or choroidal neovascularisation, begins with damage to the outer retinal cells and retinal pigment epithelium (RPE), which elicits a cascade of inflammatory and angiogenic responses leading to neovascularisation under the macula. Studies showed that oxidative damage, chronic inflammation of the RPE and complement misregulation work at different steps of this disease. After established neovascularisation, several pro- and antiangiogenic agents start to play an important role. Vascular endothelial growth factors (VEGFs) are the most specific and potent regulators of angiogenesis, which are inhibited by intravitreal injections of ranibizumab, bevacizumab, VEGF Trap, pegaptanib sodium and other agents under investigation. Pigment epithelium-derived factor, on the other hand, shows neuroprotective and antiangiogenic activities. Hepatocyte growth factor (HGF) has a mitogenic effect on a wide range of epithelial and endothelial cells, and it is inhibited by an anti-HGF monoclonal antibody. Platelet-derived growth factor is a potent chemoattractant and mitogen for both fibroblasts and retinal RPE cells, which has been inhibited experimentally by VEGF Trap and human anti-platelet-derived growth factor-D monoclonal antibody. Fibroblast growth factor-2 has pleiotropic effects in different cell and organ systems, and it is blocked by anti-FGF antibodies, with a greater benefit regarding antiangiogenesis when combined treatment with anti-VEGF is performed. Tumour necrosis factor alpha is expressed in the retina and the choroid, and its blockade in choroidal neovascularisation includes the use of monoclonals such as infliximab. This paper reviews the most important cytokines involved in the pathogenesis of wet-AMD, with emphasis on potential combined therapies for disease control.

Temperature Dependence of Coarse-grained Potentials for Liquid Hexane

Physical Chemistry Chemical Physics : PCCP. Feb, 2011  |  Pubmed ID: 21157607

The present molecular dynamics study is an investigation of the temperature (T) dependence of liquid hexane coarse-grained potentials optimized with the Iterative Boltzmann Inversion method. An approach for the derivation of coarse-grained potentials at temperatures T different from the optimization temperature T(0) has recently been proposed for ethylbenzene. This method is based on the use of a T-dependent scaling factor f(T) to generate ethylbenzene potentials at T≠T(0). The approach is here extended to hexane, considering different reference temperatures T(0) and functional forms for f(T). From our simulations, it appears that the accuracy of the temperature transferability depends simultaneously on the T(0) chosen and the analytic form of f(T). Such a behavior is suppressed by the use of a new 2-point interpolation formula to generate coarse-grained potentials as a function of T. This scheme employs a linear interpolation based on the optimization of coarse-grained potentials at two reference temperatures, T(L) and T(U), with T(L)≤T≤T(U). Accurate coarse-grained simulations of liquid hexane can be performed using the new interpolation scheme. The results are encouraging for the use of potential interpolations as a practical means for devising coarse-grained potentials within a wider temperature range.

Incidence of Rhegmatogenous Retinal Detachments After Intravitreal Antivascular Endothelial Factor Injections

Acta Ophthalmologica. Feb, 2011  |  Pubmed ID: 21176118

To determine the incidence of rhegmatogenous retinal detachments (RD) after intravitreal injection in six high-volume centres.

Acquired Protein C Deficiency in a Child with Acute Myelogenous Leukemia, Splenic, Renal, and Intestinal Infarction

Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. Mar, 2011  |  Pubmed ID: 21178585

We report the case of a 6-year-old boy diagnosed with acute promyelocytic leukemia (AML-M3V) when he presented with pallor, abdominal pain, anorexia, and fatigue. Induction chemotherapy was started according to the AML-BFM 98 protocol along with Vesanoid (ATRA, All-trans retinoic acid). On the sixth day of induction, he developed splenic and gallbladder infarcts. Splenectomy and cholecystectomy were performed while chemotherapy induction continued as scheduled. Four days later, he developed ischemic areas in the kidneys and ischemic colitis in the sigmoid colon. Hypercoagulation studies showed severe deficiency of protein C. Tests showed protein C 16% (reference range 70-140%), protein S 87% (reference range 70-140%), antithrombin III 122% (reference range 80-120%), prothrombin time 13.6 s (reference = 11.3), INR (international normalized ratio) 1.21, partial thromboplastin time 33 s (reference = 33), fibrinogen 214 mg/dl, D-dimer 970 μg/ml, factor II 98%, and that antinuclear antibody, antiphospholipid antibodies, mutation for factor II gene (G20210A), and mutation for Arg506 Gln of factor V were all negative (factor V Leiden). There was no evidence of clinical disseminated intravascular coagulation (DIC). He was treated with low molecular weight heparin and did well. He continues to be in complete remission 7 years later with normal protein C levels. Acquired protein C deficiency can occur in a variety of settings and has been reported in acute myelocytic leukemia. However, clinically significant thrombosis in the absence of clinical DIC, such as our case, remains extremely rare.

Effects of Body Mass Index on Sleep Patterns During Pregnancy

Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2011  |  Pubmed ID: 21281025

The purpose of this study was to profile sleep patterns during pregnancy according to body mass index (BMI) and to correlate labour outcomes with both BMI and hours sleep. Data were collected from 200 postpartum women detailing sleep characteristics before and during pregnancy. A validated sleep questionnaire was employed, which comprised of questions about sleep apnoea, snoring, subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication and daytime dysfunction. Descriptive analyses were used. With advancing gestation, the mean (SD) number of hours sleep per night declined: pre-pregnancy 8.1 (SD 1.4); 1st trimester 8.3 (SD 1.8); 2nd trimester 7.7 (SD 1.7) and 3rd trimester 6.7 (SD 2.2). In the 18.5-24.9 BMI group, there was a marked difference in hours sleep per night from pre-pregnancy to 1st (8.6 h, p = 0.007), 2nd (7.9 h, p = 0.023) and 3rd (6.4 h, p = 0.000) trimesters in primiparous women. In the 25-29.9 BMI group, there was a difference from pre-pregnancy to 3rd trimester (p = 0.000). These changes were not reflected in a clinically significant difference in birth weight or mode of delivery.

Reasons for Ineligibility in Phase 1 and 2A HIV Vaccine Clinical Trials at Kenya AIDS Vaccine Initiative (KAVI), Kenya

PloS One. 2011  |  Pubmed ID: 21283743

With the persistent challenges towards controlling the HIV epidemic, there is an ongoing need for research into HIV vaccines and drugs. Sub-Saharan African countries--worst affected by the HIV pandemic--have participated in the conduct of clinical trials for HIV vaccines. In Kenya, the Kenya AIDS Vaccine Initiative (KAVI) at the University of Nairobi has conducted HIV vaccine clinical trials since 2001.

Effect of Needle Type and Injection Technique on Pain Level and Vitreal Reflux in Intravitreal Injection

Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics. Apr, 2011  |  Pubmed ID: 21314588

To evaluate the amount of reflux and degree of pain with intravitreal injection (IVT) using 6 different types of syringes/needles and 5 techniques of scleral incision, including 3 modifications of a beveled scleral incision.

Randomized Clinical Trial Evaluating METDRS Versus Normal or High-density Micropulse Photocoagulation for Diabetic Macular Edema

Investigative Ophthalmology & Visual Science. Jun, 2011  |  Pubmed ID: 21345996

To compare modified Early Treatment Diabetic Retinopathy Study (mETDRS) focal/grid laser photocoagulation with normal-density (ND-SDM) or high-density (HD-SDM) subthreshold diode-laser micropulse photocoagulation for the treatment diabetic macular edema (DME).

A Novel and Practical Method Using HRP-polymer Conjugate and Microwave Treatment for Visualization of 2 Antigens Raised from the Same or Different Species in Paraffin-embedded Tissues

Applied Immunohistochemistry & Molecular Morphology : AIMM / Official Publication of the Society for Applied Immunohistochemistry. Jul, 2011  |  Pubmed ID: 21386705

Recent advances in imaging systems have improved the ability to simultaneously visualize expression of multiple antigens in a single tissue section. In most instances, fluorescence microscopy, modern imaging systems, electronic scanners, and expensive reagents are required to achieve these results. Using conventional methodologies, we have developed an inexpensive and straightforward method for visualizing 2 antigens on a single formalin-fixed paraffin-embedded tissue section. The protocol combines the use of broad spectrum horseradish peroxidase-polymer conjugate and microwave treatment for detection of 2 primary antibodies raised from the same or different species. Our technique enables the researcher to simultaneously visualize 2 antigens in paraffin-embedded tissue requiring only one enzyme and a microwave.

Anal Sex, Vaginal Practices, and HIV Incidence in Female Sex Workers in Urban Kenya: Implications for the Development of Intravaginal HIV Prevention Methods

AIDS Research and Human Retroviruses. Oct, 2011  |  Pubmed ID: 21406032

Multiple intravaginal HIV prevention methods, including microbicide gels, barriers, and intravaginal rings, are in clinical development in Africa. Development of intravaginal HIV prevention products requires an understanding of sexual behavior, sexually transmitted infection (STI), and vaginitis prevalences, and sexual and vaginal practices in potential target populations. We assessed these factors in a cohort of Kenyan female sex workers (FSW). Women who reported exchanging sex for money/gifts at least three times in the past month and who were HIV uninfected were enrolled and followed for 6 months. STI prevalence and HIV incidence were analyzed by multivariate logistic regression analysis, controlling for demographic and behavioral factors. Thirty-seven percent (74/200) reported having had anal sex. Frequency of anal sex was higher with regular and casual partners than with primary partners. Women were less likely to use condoms for anal sex than for vaginal sex with regular or casual partners. Vaginal washing was universal (100%). HIV incidence was 5.6 per 100 person-years (95% CI 1.62, 11.67). HIV incidence was not associated with any demographic or risk behavior. The relatively high rate of anal sex and universal vaginal washing may complicate both safety and efficacy evaluation of intravaginal products and should be taken into account in trial design. This FSW population had significant HIV incidence and needs continued HIV prevention interventions.

Structure-function Analysis of the HrpB2-HrcU Interaction in the Xanthomonas Citri Type III Secretion System

PloS One. 2011  |  Pubmed ID: 21408079

Bacterial type III secretion systems deliver protein virulence factors to host cells. Here we characterize the interaction between HrpB2, a small protein secreted by the Xanthomonas citri subsp. citri type III secretion system, and the cytosolic domain of the inner membrane protein HrcU, a paralog of the flagellar protein FlhB. We show that a recombinant fragment corresponding to the C-terminal cytosolic domain of HrcU produced in E. coli suffers cleavage within a conserved Asn264-Pro265-Thr266-His267 (NPTH) sequence. A recombinant HrcU cytosolic domain with N264A, P265A, T266A mutations at the cleavage site (HrcU(AAAH)) was not cleaved and interacted with HrpB2. Furthermore, a polypeptide corresponding to the sequence following the NPTH cleavage site also interacted with HrpB2 indicating that the site for interaction is located after the NPTH site. Non-polar deletion mutants of the hrcU and hrpB2 genes resulted in a total loss of pathogenicity in susceptible citrus plants and disease symptoms could be recovered by expression of HrpB2 and HrcU from extrachromossomal plasmids. Complementation of the ΔhrcU mutant with HrcU(AAAH) produced canker lesions similar to those observed when complemented with wild-type HrcU. HrpB2 secretion however, was significantly reduced in the ΔhrcU mutant complemented with HrcU(AAAH,) suggesting that an intact and cleavable NPTH site in HrcU is necessary for total functionally of T3SS in X. citri subsp. citri. Complementation of the ΔhrpB2 X. citri subsp. citri strain with a series of hrpB2 gene mutants revealed that the highly conserved HrpB2 C-terminus is essential for T3SS-dependent development of citrus canker symptoms in planta.

Comparison of 20-, 23-, and 25-gauge Air Infusion Forces

Retina (Philadelphia, Pa.). Nov, 2011  |  Pubmed ID: 21673614

To determine and compare 20-, 23-, and 25-gauge retinal infusion air jet impact pressure (force per unit area) in an experimental setting.

Probing Metabolic Stability of CdSe Nanoparticles: Alkaline Extraction of Free Cadmium from Liver and Kidney Samples of Rats Exposed to CdSe Nanoparticles

Journal of Hazardous Materials. Aug, 2011  |  Pubmed ID: 21700388

Cadmium selenide nanoparticles (CdSe NPs) exhibit novel optoelectronic properties for potential biomedical applications. However, their metabolic stability is not fully understood because of the difficulties in measurement of free Cd from biological tissues of exposed individuals. In this study, alkaline dissolution with tetramethylammonium hydroxide (TMAH) is demonstrated for selective determination of free Cd and intact NPs from liver and kidney samples of animals that were exposed to thiol-capped CdSe NPs. Aqueous suspensions of CdSe NPs (3.2 nm) were used to optimize the conditions for extracting free Cd without affecting NPs. Nanoparticles were found to aggregate when heated in TMAH without releasing any significant Cd to solution. Performance of the method in discriminating free Cd and intact NPs were verified by Dogfish Liver (DOLT-4) certified reference material. The samples from the animals were digested in 4 mL TMAH at 70°C to extract free Cd followed by analysis of aqueous phase by ICP-MS. Both liver and kidney contained significant levels of free Cd. Total Cd was higher in the liver, while kidney accumulated mostly free Cd such that up to 47.9% of total Cd in the kidney was free Cd when NPs were exposed to UV-light before injection.

Multiple Primary Malignancies: Analysis of 23 Patients with at Least Three Tumors

Journal of Gastrointestinal Cancer. Jun, 2011  |  Pubmed ID: 21706155

BACKGROUND: There is scarcity of reports addressing patients with three or more malignancies. The aim of this study is to present a detailed analysis of patients presenting with at least three primary malignant tumors. PATIENTS AND METHODS: Records of cancer patients presenting to King Hussein Cancer Center (Amman, Jordan) between June 2006 and March 2011 were retrospectively reviewed. Patients harboring multiple primary tumors were included for detailed analysis. Data relating to epidemiological features, pathological characteristics, and disease outcomes were extracted. RESULTS: Out of 14,040 cases, 319 patients (2.3%) harbored two or more while 23 patients (0.16%) harbored three or more primary malignant tumors. This study included 17 males and six females between 4 and 78 years of age (median, 52 years) at the time of diagnosis of the first malignancy. The most prevalent tumor was colorectal adenocarcinoma found in nine, followed by lymphoma in seven, and prostate adenocarcinoma in six patients. The most common tumor combinations were colorectum-non-melanoma skin, colorectum-kidney, and non-melanoma skin-kidney all found in four patients, respectively. At a median follow-up of 96 months from the time of diagnosis of the first primary (range, 2-337 months) and 8 months from the time of diagnosis of the last primary (range, 1-48 months), 13 were alive with no evidence of disease, six were alive with residual disease, three were dead due to disease, and one patient was alive with unknown disease status. CONCLUSIONS: The possibility of multiple primary malignancies should always be considered during the treatment and follow-up of cancer patients. This case series could prove helpful to clinicians faced with similar, however, exceedingly rare scenarios. Due to the realistic potential for long-term survival, we recommend aggressive treatment of these patients.

3H-L-leucine Transport by the Promiscuous Crustacean Dipeptide-like Cotransporter

Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology. Oct, 2011  |  Pubmed ID: 21732547

The crustacean intestine and hepatopancreas display a variety of solute transport mechanisms for transmembrane transfer of dietary contents from lumen to epithelial cytosol. An in vitro intestinal perfusion apparatus was used to characterize mucosal to serosoal (MS) and serosal to mucosal (SM) Zn(2+) -dependent (3)H-L-leucine transport by the intestine of the American lobster, Homarus americanus. Transmural 20 µM MS (3)H-L-leucine fluxes across lobster intestine were a hyperbolic function of luminal zinc concentration (1-50 µM) following Michaelis-Menten kinetics (K(m) = 2.67 ± 0.74 µM; J(max) = 19.56 ± 2.22 pmol/cm(2) ×min). Transmural 20 µM SM (3)H-L-leucine fluxes were not affected by serosal zinc, resulting in a highly significant stimulation of net amino acid transfer to the blood by luminal metal. MS fluxes of 20 µM (3)H-L-leucine were also hyperbolic functions of luminal [Cu(2+)], [Mn(2+)], [Na(+)], and [H(+)]. MS flux of (3)H-L-leucine was a sigmoidal function of luminal [L-leucine] and was stimulated by the addition of 20 µM luminal zinc at both pH 7.0 and 5.5. A greater enhanced amino acid transport occurred at the lower pH 5.5. MS flux of 20 µM (3)H-L-leucine in the presence of 20 µM zinc was significantly inhibited by addition of 100 µM luminal glycylsarcosine, and MS flux of 20 µM (3)H-glycylsarcosine was inhibited by 100 µM L-leucine in the presence of 20 µM zinc. Results suggest that (3)H-L-leucine and metals form a complex (e.g., Leu-Zn-Leu] that may functionally mimic dipeptides and use a dipeptide-like transporter during MS fluxes as suggested for fish and mammals.

Fundus Autofluorescence and Spectral Domain OCT in Central Serous Chorioretinopathy

Journal of Ophthalmology. 2011  |  Pubmed ID: 21845214

Background. To describe the standard autofluorescence (FAF), the near infrared autofluorescence (NIA) and optical coherence tomography (OCT) patterns in central serous chorioretinopathy, correlating them with fluorescein angiography. Methods. Cross-sectional observational study, in which patients with at least seven months of CSC underwent ophthalmologic examination, fundus photography, FAF, NIA, fluorescein angiography (FA), and spectral-domain OCT. Results. Seventeen eyes of thirteen patients were included. The presentation features were a mottled hyperFAF in the detached area and areas with pigment mottling. NIA images showed areas of hyperNIA similar to FAF and localized areas of hypoNIA, which correlated with the points of leakage in the FA. OCT showed pigment epithelium detachment at the location of these hypoNIA spots. Discussion. FAF showed increased presence of fluorophores in the area of retinal detachment, which is believed to appear secondary to lipofuscin accumulation in the RPE or the presence of debris in the subretinal fluid. NIA has been related to the choroidal melanin content and there were areas of both increased and decreased NIA, which could be explained by damage ahead the retina, basically RPE and choroid. These findings, along with the PEDs found in the areas of hypoNIA, support the notion of a primary choroidal disease in CSC.

Discussing Smart Pills Versus Endorsing Smart Pills: Reply to Swanson, Wigal, and Volkow (2011) and Elliott and Elliott (2011)

Psychological Bulletin. Sep, 2011  |  Pubmed ID: 21859177

We find much of interest, and little to disagree with, in the commentaries on our article. We take issue only with the suggestion that our article was provocative and submit that the attempt to understand the use of stimulants as smart pills does not imply an endorsement of the practice.

Ethanol Causes the Redistribution of L1 Cell Adhesion Molecule in Lipid Rafts

Journal of Neurochemistry. Nov, 2011  |  Pubmed ID: 21884525

Fetal alcohol spectrum disorder is estimated to affect 1% of live births. The similarities between children with fetal alcohol syndrome and those with mutations in the gene encoding L1 cell adhesion molecule (L1) implicates L1 as a target of ethanol developmental neurotoxicity. Ethanol specifically inhibits the neurite outgrowth promoting function of L1 at pharmacologic concentrations. Emerging evidence shows that localized disruption of the lipid rafts reduces L1-mediated neurite outgrowth. We hypothesize that ethanol impairment of the association of L1 with lipid rafts is a mechanism underlying ethanol's inhibition of L1-mediated neurite outgrowth. In this study, we examine the effects of ethanol on the association of L1 and lipid rafts. We show that, in vitro, L1 but not N-cadherin shifts into lipid rafts following treatment with 25 mM ethanol. The ethanol concentrations causing this effect are similar to those inhibiting L1-mediated neurite outgrowth. Increasing chain length of the alcohol demonstrates the same cutoff as that previously shown for inhibition of L1-L1 binding. In addition, in cerebellar granule neurons in which lipid rafts are disrupted with methyl-beta-cyclodextrin, the rate of L1-mediated neurite outgrowth on L1-Fc is reduced to background rate and that this background rate is not ethanol sensitive. These data indicate that ethanol may inhibit L1-mediated neurite outgrowth by retarding L1 trafficking through a lipid raft compartment.

Plasminogen Activator Inhibitor Type 1 Serum Levels and 4G/5G Gene Polymorphism in Morbidly Obese Hispanic Patients with Non-alcoholic Fatty Liver Disease

Annals of Hepatology. Oct-Dec, 2011  |  Pubmed ID: 21911891

The plasminogen activator inhibitor type-1 (PAI-1) has been implicated in the regulation of fibrinolysis and extracellular matrix components. The single base pair guanine insertion/deletion polymorphism (4G/5G) within the promoter region of the PAI-1 gene influences PAI-1 synthesis and may modulate hepatic fibrogenesis.

A Comprehensive Approach to CT Radiation Dose Reduction: One Institution's Experience

AJR. American Journal of Roentgenology. Oct, 2011  |  Pubmed ID: 21940582

OBJECTIVE: The purpose of this article is to review the process of creating and implementing a comprehensive plan to reduce diagnostic radiation exposure at our institution. CONCLUSION: This process, which was initiated by forming a radiation dose reduction committee, addressed several different issues to improve patient safety. These include avoidance of unnecessary CT examinations, adjusting individual scanning parameters, revising protocols, use of shielding and dose monitoring, and implementing computer-based dose modulation software as well as educating referring physicians and radiologic technologists.

Congenital Absence of Hepatic Segment IV-V in Symptomatic Huge Abdominal Cyst: an Intraoperative Anatomic Liver Finding Never Described in the Literature

The American Surgeon. Sep, 2011  |  Pubmed ID: 21944598

Serotonin Transporter Genotype Modulates the Association Between Depressive Symptoms and Amygdala Activity Among Psychiatrically Healthy Adults

Psychiatry Research. Sep, 2011  |  Pubmed ID: 21764567

Recent attempts to understand the biological bases of depression vulnerability have revealed that both the short allele of the serotonin transporter-linked polymorphic region (5-HTTLPR) and activity in the amygdala are associated with depression. Other studies have reported amygdala hyperactivity associated with the 5-HTTLPR short allele, linking the genetic and neuroimaging lines of research and suggesting a mechanism whereby the short allele confers depression risk. However, fewer investigations have examined the associations among depression, 5-HTTLPR variability, and amygdala activation in a single study. The current study thus investigated whether 5-HTTLPR genotype modulates the association between depressive symptoms and amygdala activity among psychiatrically healthy adults. Regional cerebral blood flow was measured with perfusion fMRI during a task-free scan. We hypothesized differential associations between depressive symptoms and amygdala activity among individuals homozygous for the short allele and individuals homozygous for the long allele. Both whole brain analyses and region-of-interest analyses confirmed this prediction, revealing a significant negative association among the long allele group and a trend of positive association among the short allele group. These results complement existing reports of short allele related amygdala hyperactivity and suggest an additional neurobiological mechanism whereby the 5-HTTLPR is associated with psychiatric outcomes.

The Potential Neuroprotective Effects of Weekly Treatment with Glatiramer Acetate in Diabetic Patients After Panretinal Photocoagulation

Clinical Ophthalmology (Auckland, N.Z.). 2011  |  Pubmed ID: 21792290

Evaluation of the neuroprotective effect of weekly glatiramer acetate (GA) on retinal structure and function in diabetic patients who underwent panretinal photocoagulation (PRP).

Maternity Services for Obese Women in Ireland

Irish Medical Journal. Jul-Aug, 2011  |  Pubmed ID: 21957691

Nearly one in five women booking for antenatal care in Ireland is obese. The purpose of this survey was to audit the services and facilities for obese pregnant women in the country's maternity units. In June 2010, a detailed questionnaire was sent to all 20 units which included questions on services, equipment and facilities for obese women. All 20 units responded: 17 (85%) were calculating and recording Body Mass Index in pregnancy. Only 15 (75%) were screening obese women for gestational diabetes mellitus and 2 (10%) were omitting thromboprophylaxis for caesarean section in obese women. Only 3 (15%) had clinical guidelines for obesity and pregnancy. The facilities and equipment, particularly for severely obese women, were inadequate in the majority of units. This survey showed variations nationally in obstetric practices and facilities. It highlights the need to develop, disseminate and implement standardised guidelines on maternal obesity.

Posterior Chordal Cutting in Rheumatic Mitral Regurgitation Due to Hypomobility of the Posterior Leaflet

The Annals of Thoracic Surgery. Oct, 2011  |  Pubmed ID: 21958818

A technique is described for correction of mitral regurgitation when the posterior leaflet has a reasonable length (approximately 10 mm), but its movements are limited by thickened and short chords. To avoid further retraction when a band or a ring is positioned to force leaflets coaptation, native chords are replaced by artificial chords (leaving 10 mm of extra length), which are then cut. In 6 patients, after 6 months of follow-up, the results are good.

Neutrophil-lymphocyte Ratio As a Predictor of Adverse Outcomes of Acute Pancreatitis

Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]. 2011  |  Pubmed ID: 21968329

Most acute pancreatitis risk scoring systems use total white blood cell counts (WBC) as one of the risk factors. The value of the neutrophil-lymphocyte ratio (NLR) to predict the severity of acute pancreatitis has not been previously evaluated.

A New Mechanism of Action of a C2 Domain-derived Novel PKC Inhibitor Peptide

Neuroscience Letters. Oct, 2011  |  Pubmed ID: 21982802

Novel protein kinase Cs (nPKCs) contain an N-terminal C2 domain that cannot bind to calcium. We have previously shown that the Aplysia novel PKC Apl II's C2 domain inhibits binding of diacylglycerol (DAG) to the C1 domain and that this inhibition is removed by phosphatidic acid (PA) binding to the C1b domain. Another model for C2 domain regulation of nPKCs suggests that the C2 domain binds to receptors for activated C kinase (RACKs) to assist in kinase translocation and activation. In the present study, we examined how a pharmacological peptide derived from RACK-binding site in the vertebrate novel PKCɛ regulates translocation of PKC Apl II from the cytosol to the plasma membrane. We found that a C2 domain-derived inhibitor peptide inhibited PKC Apl II translocation. This inhibition was removed by R273H mutation in the C1b domain and by phosphatidic acid, which can both remove C2-domain mediated inhibition suggesting that the peptide can regulate C1-C2 domain interactions.

Waist Circumference in the First Trimester As a Predictor of Caesarean Section

European Journal of Obstetrics, Gynecology, and Reproductive Biology. Dec, 2011  |  Pubmed ID: 21992963

Use of Electron-beam Sterilized Hemodialysis Membranes and Risk of Thrombocytopenia

JAMA : the Journal of the American Medical Association. Oct, 2011  |  Pubmed ID: 22009100

Thrombocytopenia is not widely recognized as a potential dialyzer-related complication. Following the observation of significant thrombocytopenia among 20 patients undergoing hemodialysis in a single dialysis unit after the introduction of dialyzers sterilized by electron beam (e-beam), a larger investigation was undertaken.

Semi-field Evaluation of Several Novel Alkenol Analogs of 1-octen-3-ol As Attractants to Adult Aedes Albopictus and Culex Quinquefasciatus

Journal of the American Mosquito Control Association. Sep, 2011  |  Pubmed ID: 22017090

The compound 1-octen-3-ol is a known attractant of some mosquito species, which has led to the hypothesis that olfactory stimulation by this alkenol may be associated with the following structural elements: a terminal site of unsaturation or high electron density; a structural capability for hydrogen bonding, e.g., -OH, -NH2, NHR, NR2, etc.; a saturated hydrocarbon chain of a certain minimum length; and a certain relative distance between the region of high electron density and the alcohol (or other hydrogen-bonding) functional group. Using this logic, we synthesized 20 alkenol analogs based on the octenol double-bonded carbon skeleton. The attraction of female Aedes albopictus and Culex quinquefasciatus to these analogs was compared with 1-octen-3-ol as a standard in semi-field trials. For both species, collections from Mosquito Magnet-X (MMX) suction traps baited with the alkenol analogs in the absence of carbon dioxide were not significantly different from octenol-only baited traps, with the exception of (Z)-3-hepten-1-ol which collected significantly more Ae. albopictus. In the presence of CO2, most of the collections from traps baited with an alkenol were considerably increased for both species but not different from octenol plus CO2, with the exception of Ae. albopictus where (Z)-3-decen-1-ol, (Z)-4-hexen-1-ol, 7-octen-2-ol, and 8-nonen-3-ol significantly depressed trap catches. Although no clearly identifiable structure-activity relationship could be determined from our collected data, we did find that MMX traps baited with carbon dioxide and 4-penten-2-ol or (E)-2-decen-4-ol significantly enhanced Cx. quinquefasciatus collections up to nearly 3-fold compared with octenol plus carbon dioxide.

Parent-adolescent Relationships and Social Adjustment: the Case of a Collectivistic Culture

International Journal of Psychology : Journal International De Psychologie. Jun, 2011  |  Pubmed ID: 22044231

This study examined how parent-adolescent relationships are related to adolescent loneliness, interpersonal difficulties and school adjustment among Israeli Arabs. Two hundred and thirty-one 11th graders (103 boys and 128 girls) and their homeroom teachers participated. Four groups of adolescents were identified according to parenting practice profiles: Adolescents in the harsh parenting group reported the highest levels of loneliness, those in the distant and mixed groups reported midway levels of loneliness, and those in the warm group showed the lowest degree of loneliness and the lowest levels of interpersonal problems. Overall, boys reported higher levels of peer-related loneliness and lower levels of affinity for aloneness than girls. Gender interacted significantly with parenting group, with girls in the harsh parenting group exhibiting greater parent-related loneliness and affinity for loneliness, while boys exhibited more peer-related loneliness. The important role that parents play in their children's social adjustment is discussed in relation to gender and culture.

Biodegradable Polymers Derived from Amino Acids

Macromolecular Bioscience. Dec, 2011  |  Pubmed ID: 22052719

In the past three decades, the use of polymeric materials has increased dramatically for biomedical applications. Many α-amino acids derived biodegradable polymers have also been intensely developed with the main goal to obtain bio-mimicking functional biomaterials. Polymers derived from α-amino acids may offer many advantages, as these polymers: (a) can be modified further to introduce new functions such as imaging, molecular targeting and drugs can be conjugated chemically to these polymers, (b) can improve on better biological properties like cell migration, adhesion and biodegradability, (c) can improve on mechanical and thermal properties and (d) their degradation products are expected to be non-toxic and readily metabolized/excreted from the body. This manuscript focuses on biodegradable polymers derived from natural amino acids, their synthesis, biocompatibility and biomedical applications. It is observed that polymers derived from α-amino acids constitute a promising family of biodegradable materials. These provide innovative multifunctional polymers possessing amino acid side groups with biological activity and with innumerous potential applications.

[Erectile Dysfunction in Polycythemia Vera.]

Presse Medicale (Paris, France : 1983). Nov, 2011  |  Pubmed ID: 22056779

Virulence Characteristics and Antimicrobial Susceptibility of Uropathogenic Escherichia Coli Strains

Genetics and Molecular Research : GMR. Oct, 2011  |  Pubmed ID: 22057993

Eight virulence factors associated with uropathogenic Escherichia coli (UPEC) were investigated in 204 clinical isolates of E. coli recovered from urine cultures at counts ≥10(5). The bacteria were classified into two groups according to the number of leukocytes in urine samples from which they were isolated: group I ≤8 leukocytes/hpf, 104 strains; group II >8 leukocytes/hpf, 100 strains. Two multiplex PCR systems were used to detect genes encoding adhesin P (pap), adhesin S (sfa), afimbrial adhesin I (afa), siderophore aerobactin (aer), alpha-hemolysin (hly), cytotoxic necrotizing factor type 1 (cnf1), and traT associated with serum resistance. The PAI marker for the virulence island identified in strains CFT072 and CVD432, a marker of enteroaggregative E. coli, was also investigated using PCR. The susceptibility profile of E. coli strains was determined by disk diffusion method. Ninety percent UPEC showed at least one of the virulence genes, the prevalence being traT (76%), aer (41%), PAI (32%), sfa (26%), pap (25%), cnf1 (18%), afa (6%), and hly (5%). There was no significant difference in the distribution of virulence genes between groups I and II. A significantly higher degree of virulence was detected in UPEC group II. The CVD432 gene was not detected in any of the UPECs. Fifty-nine percent of the strains were resistant to at least one of the antimicrobials that we tested; the most common being resistance to ampicillin (51%) and trimethoprim-sulfamethoxazole (44%).

Testing the Educational Potential of 3D Visualization Software in Oral Radiographic Interpretation

Journal of Dental Education. Nov, 2011  |  Pubmed ID: 22058390

There is heightened optimism about the potential of 3D visualization software as an alternative learning resource in radiology education. The purpose of this study was to investigate the effect of 3D visualization software on students' learning of oral radiographic interpretation from 2D radiographic images. Fourth-year dental students underwent a learning intervention phase of radiographic interpretation of oral pathoses using 3D visualization software. The success of the educational intervention was assessed by quantitative means, using a radiographic interpretation test, and by qualitative means, using a structured Likert-scale survey, asking students to evaluate their own learning outcomes. It was anticipated that training with the rotational mode of 3D visualization software would provide additional depth cues, enabling students to create spatial-mental models of anatomy that they can apply to 2D radiographic interpretation of oral pathoses. Although quantitative assessment did not support this, questionnaire evaluations demonstrated a positive effect of the 3D visualization software by enhancing students' learning about radiographic interpretation. Despite much optimism about the educational potential of 3D visualization software, it is important to understand the interactions between learners and such new technologies in order to identify potential advantages and limitations prior to embracing them as learning resources.

Educational Differences in Disability Pension Among Swedish Middle-aged Men: Role of Factors in Late Adolescence and Work Characteristics in Adulthood

Journal of Epidemiology and Community Health. Nov, 2011  |  Pubmed ID: 22068029

BackgroundThe association between level of education and disability pension (DP) is well known. Earlier studies have investigated the importance of early life factors and work characteristics but not in combination. The aim of this study was to investigate the association between level of education and DP among Swedish middle-aged working men and to what extent such an association can be explained by factors measured in late adolescence and work characteristics in adulthood.MethodsInformation about IQ, health-related lifestyle factors, psychiatric and musculoskeletal diagnoses was obtained from the 1969 conscription cohort, consisting of 49 321 Swedish men. Data collected when subjects were 18-20 years of age were combined with national register-based information about level of education, job control and physical strain at work in adulthood, and information about DP between 1991 and 2002.ResultsThere was a strong graded association between level of education and DP. Those with the lowest level of education had a four times greater probability of having DP as compared with those with the highest level. In multivariable analyses, factors measured in late adolescence, IQ in particular, attenuated the association more than work-related characteristics in adulthood.ConclusionsThe authors found an association between level of education and DP among Swedish middle-aged working men. A large part of the association was explained by factors measured in late adolescence, IQ in particular, and somewhat less by work characteristics measured in adulthood. Level of education remained as a significant predictor of DP in middle age after full adjustment.

Toxicity and Retinal Penetration of Infliximab in Primates

Retina (Philadelphia, Pa.). Mar, 2012  |  Pubmed ID: 22080907

To evaluate the retinal penetration and toxicity of two doses of intravitreal infliximab in primates.

Timing of Screening for Gestational Diabetes Mellitus in Women with Moderate and Severe Obesity

Acta Obstetricia Et Gynecologica Scandinavica. Apr, 2012  |  Pubmed ID: 22085417

Objective. We evaluated screening with a diagnostic oral glucose tolerance test earlier than 20 weeks gestation in women with moderate to severe obesity. Design. Prospective observational study. Setting. Large university teaching hospital. Population. We enrolled 100 women booking for antenatal care in the first trimester at their convenience. Methods. Height and weight were measured and body mass index calculated. Only women with a body mass index>34.9 kg/m(2) were included. Women were booked for a 100 g oral glucose tolerance test before 20 weeks and, if normal, another test at 28 weeks gestation. Main outcome measures. Impaired glucose tolerance and gestational diabetes mellitus. Results. Of the 100 women given an appointment for an oral glucose tolerance test before 20 weeks gestation, 92 attended. Of these, 10 (10.8%) women had an abnormal result, with impaired glucose tolerance in five (5.4%) cases and gestational diabetes mellitus in five (5.4%) cases. Of those with a normal result at 20 weeks, 81 attended for a repeat test at 28 weeks gestation. A further four (4.9%) had impaired glucose tolerance and four (4.9%) had gestational diabetes mellitus. A total of 18 (20.5%) of the 88 women who complied with screening had an abnormal test. Conclusions. Women who have moderate/severe obesity have a one in five chance of having an abnormal diagnostic oral glucose tolerance test when screened for gestational diabetes mellitus. To optimize maternal glycemic control in pregnancy, we suggest that women with a body mass index>34.9 kg/m(2) may need to be screened early in pregnancy and, if the test is normal, again at 28 weeks gestation.

Timing of Fructose Intake: an Important Regulator of Adiposity

Clinical and Experimental Pharmacology & Physiology. Jan, 2012  |  Pubmed ID: 22032284

1. Overconsumption of fructose produces glucose intolerance, autonomic abnormalities and renal dysfunction and may be related to the worldwide epidemic of obesity and diabetes. 2. Experiments were conducted to determine whether the time period (light or dark) of fructose consumption influenced the pathological consequences. C57BL mice were given standard chow and assigned to one of three groups: (i) control (n = 10), which received water over a 24 h period; (ii) FL (n = 11), which received 10% fructose solution during the 12 h light period; and (iii) FD (n = 11), which received 10% fructose solution during the 12 h dark period. 3. There was a time related increase in body weight for all groups (P < 0.01, 2 vs 6 wks). There was a greater increase in body fat in the FL group compared with the control and FD groups. The changes in adiposity occurred even though the total caloric intake was not significantly different among the groups (approximately 18 kcal/day). Total fluid (water + fructose) consumption was greater in the FD and FL groups compared with control at 6 weeks. Significant increases were noted for plasma insulin and leptin at 8 weeks, with highest levels in the FL compared with FD group (P < 0.05). There were no significant changes in glucose, glucose tolerance, cholesterol, triglycerides or adiponectin. 4. The results of the present study suggest that there is a mismatch in caloric consumption, metabolism and adiposity as related to the light-dark cycle of fructose consumption. These findings have clinical implications in the control of bodyweight, abdominal fat accumulation and Type 2 diabetes.

Inhibitory Responses in Aplysia Pleural Sensory Neurons Act to Block Excitability, Transmitter Release, and PKC Apl II Activation

Journal of Neurophysiology. Jan, 2012  |  Pubmed ID: 21994260

Expression of the 5-HT(1Apl(a)) receptor in Aplysia pleural sensory neurons inhibited 5-HT-mediated translocation of the novel PKC Apl II in sensory neurons and prevented PKC-dependent synaptic facilitation at sensory to motoneuron synapses (Nagakura et al. 2010). We now demonstrate that the ability of inhibitory receptors to block PKC activation is a general feature of inhibitory receptors and is found after expression of the 5-HT(1Apl(b)) receptor and with activation of endogenous dopamine and FMRFamide receptors in sensory neurons. Pleural sensory neurons are heterogeneous for their inhibitory response to endogenous transmitters, with dopamine being the most prevalent, followed by FMRFamide, and only a small number of neurons with inhibitory responses to 5-HT. The inhibitory response is dominant, reduces membrane excitability and synaptic efficacy, and can reverse 5-HT facilitation at both naive and depressed synapses. Indeed, dopamine can reverse PKC translocation during the continued application of 5-HT. Reversal of translocation can also be seen after translocation mediated by an analog of diacylglycerol, suggesting inhibition is not through blockade of diacylglycerol production. The effects of inhibition on PKC translocation can be rescued by phosphatidic acid, consistent with the inhibitory response involving a reduction or block of production of this lipid. However, phosphatidic acid could not recover PKC-dependent synaptic facilitation due to an additional inhibitory effect on the non-L-type calcium flux linked to synaptic transmission. In summary, we find a novel mechanism downstream of inhibitory receptors linked to inhibition of PKC activation in Aplysia sensory neurons.

Using a Novel Computer-based Approach to Assess the Acute Effects of Exercise on Appetite-related Measures

Appetite. Feb, 2012  |  Pubmed ID: 21983050

Measuring food intake using standard buffet meals can be complicated by sensory and external cues which can alter energy intake. The present study was designed to examine the effects of acute exercise on non-metabolic factors related to appetite and food intake using a computer-based assessment. Twenty-seven men and women participated in two sessions in random order: 60-min walking on the treadmill (exercise trial; EX) or seated rest (control trial; CON). Subjective hunger and fullness, food liking, food utility, and ideal portion size were assessed before and immediately after exercise or rest, and hourly for 2 h. The findings showed that an acute bout of moderate intensity exercise had an anorexigenic effect; characterised by diminished hunger (-17.4%, p=0.004) and lower prospective ideal portion size (-7.7%, p=0.003) compared to no exercise. This novel, computer-based assessment, is a useful alternative to buffet meals setting and allows for the determination of non-metabolic factors associated with feeding behaviour in relation to exercise.

Asthma and Obesity: A Known Association but Unknown Mechanism

Respirology (Carlton, Vic.). Apr, 2012  |  Pubmed ID: 21992497

The obese asthma phenotype is an increasingly common encounter in our clinical practice. Epidemiological data indicate that obesity increases the prevalence and incidence of asthma, and evidence that obesity precedes the development of asthma raises the possibility of a causal association. Obese patients with asthma experience more symptoms and increased morbidity compared with non-obese asthma patients. Despite more than a decade of research into this association, the exact mechanisms that underlie the interaction of obesity with asthma remain unclear. It is unlikely that the asthma-obesity association is simply due to comorbidities such as obstructive sleep apnoea or gastroesophageal reflux disease. Although inflammatory pathways are purported to play a role, there is scant direct evidence in humans that systemic inflammation modulates the behaviour of the asthmatic airway or the expression of symptoms in the obese. The role of non-eosinophilic airway inflammation also requires further study. Obesity results in important changes to the mechanical properties of the respiratory system, and these obesity-related factors appear to exert an additive effect to the asthma-related changes seen in the airways. An understanding of the various physiological perturbations that might be contributing to symptoms in obese patients with asthma will allow for a more targeted and rational treatment approach for these patients.

Stent Implantation in Aorto-ostial Lesions: Long-term Follow-up and Predictors of Outcome

EuroIntervention : Journal of EuroPCR in Collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. Jan, 2012  |  Pubmed ID: 21959084

To compare the outcomes of drug-eluting (DES) vs. bare-metal (BMS) stents for stenting of native aorto-ostial lesions (AOL) and to identify predictors of major adverse cardio and cerebrovascular events (MACCE).

Three-year Safety and Visual Acuity Results of Epimacular 90 Strontium/90 Yttrium Brachytherapy with Bevacizumab for the Treatment of Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration

Retina (Philadelphia, Pa.). Jan, 2012  |  Pubmed ID: 21817963

To evaluate the long-term safety and visual acuity outcomes associated with epimacular strontium 90 brachytherapy combined with intravitreal bevacizumab for the treatment of subfoveal choroidal neovascularization because of age-related macular degeneration.

Prospective Risk of Fetal Death in Uncomplicated Monochorionic Twins

Acta Obstetricia Et Gynecologica Scandinavica. Mar, 2012  |  Pubmed ID: 21950601

A retrospective cohort study was carried out in a university teaching hospital to determine the prospective risk of unexpected fetal death in uncomplicated monochorionic diamniotic (MCDA) twin pregnancies after viability. All MCDA twins delivered at or after 24 weeks' gestation from July 1999 to July 2007 were included. Pregnancies with twin-twin transfusion syndrome, growth restriction, structural abnormalities, or twin reversed arterial perfusion sequence were excluded. Of the 144 MCDA twin pregnancies included in our analysis, the risk of intrauterine death was 4.9%. The prospective risk of unexpected intrauterine death was 1 in 43 after 32 weeks' gestation and 1 in 37 after 34 weeks' gestation. Our results demonstrate that despite close surveillance, the unexpected intrauterine death rate in uncomplicated MCDA twin pregnancies is high. This rate seems to increase after 34 weeks' gestation, suggesting that a policy of elective preterm delivery warrants evaluation.

Uptake and Outcome of Assisted Reproductive Techniques in Long-term Survivors of SCT

Bone Marrow Transplantation. Apr, 2012  |  Pubmed ID: 21743501

We have audited the invitation for uptake and outcome of artificial reproductive techniques in patients undergoing SCT for haematological malignancy, with the aim of improving our pre-transplant counselling. A postal survey was sent to 434 patients in our centre surviving a minimum of 2 years after allo-SCT, of whom 221 patients responded. Of 112 male patients, 79 were offered sperm storage, 42 banked sperm and 25 subsequently attempted parenthood with stored sperm. A total of 18 were successful, with 29 children born a median of 8 years (range 1-22 years) following SCT. Of 72 females <42 years old, 33 were offered storage of embryos/eggs/ovarian tissue and 12 accepted. Following SCT, four women attempted pregnancy using cryopreserved embryos, with two successes. The majority of patients who were not counselled about infertility or not offered fertility-preservation options provided a likely reason, with completion of family being the most frequent. Nonetheless, 16 patients (11/72 women and 5/112 men) could not provide a reason for the lack of information/invitation. In conclusion, uptake of gamete/embryo storage is high when offered and collected material is used frequently. Pregnancies in partners of male patients were usually successful and our data highlight the value of prolonged cryostorage.

Risk Factors for Symptoms of Gastrointestinal Illness in Rural Town Isiolo, Kenya

Zoonoses and Public Health. Mar, 2012  |  Pubmed ID: 21824377

This study assesses risk factors for food-borne gastrointestinal illness indicated by diarrhoea and/or vomiting using 14-day recalls among children and young adults. The study was set in Isiolo, a rural town of Kenya, inhabited mainly by pastoralists of different ethnic groups. The preparation methods of milk at the household level were also investigated. The study was cross-sectional and involved 900 participants from randomly selected households. They were interviewed using a structured questionnaire. An unmatched nested case-control study was constructed by randomly selecting three controls for each case. Potential risk factors for gastrointestinal illness were analysed using both univariate and multivariate logistic regression models with random effect on ethnic groups. The study results showed that consumption of mutton, carrots, Irish potatoes, raw camel milk, boiled camel milk and fermented camel milk were important risk factors for diarrhoea and/or vomiting, whereas the consumption of boiled goat milk, boiled cow milk, spinach, washing of hands with soap and the presence of proper drainage system had protective effects (odds ratio < 1). We conclude that in this setting, primarily vegetables and the camel milk market chain pose the greatest risks for symptoms of food-borne gastrointestinal illness.

Targeting Airway Remodelling in Asthma: the How, What and Where?

Respirology (Carlton, Vic.). Mar, 2012  |  Pubmed ID: 22404252

Airway remodelling in asthma remains topical in research and clinical practice, and a very poorly understood abnormality despite a large body of published work. It is important both from a pathophysiological and patient management point of view since there is evidence that airway remodelling relates to airway hyperresponsiveness (1), to accelerated lung function decline resulting in fixed airway obstruction (2) and severe disease defined by suboptimal symptom control despite high doses of inhaled corticosteroids (3). One of the major difficulties in studying and understanding airway remodelling in relation to disease mechanisms and clinical expression is the inherent problems in its measurement. It is arguable whether histopathology should be the gold standard for airway remodelling. Nevertheless, measurements from post-mortem studies show that remodelling is present in airways of all sizes and that the severity of remodelling in large airways is indeed reflective of that in the small cartilaginous airways (4). Airway remodelling is worse in patients who have fatal asthma compared to the lungs of patients who have milder stable asthma (5). However, bronchial biopsy is very difficult to undertake in longitudinal studies and therefore, is not suitable for intervention studies in large cohorts. © 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.

Changes in Breathing Pattern and Thoracoabdominal Motion After Bariatric Surgery: A Longitudinal Study

Respiratory Physiology & Neurobiology. Mar, 2012  |  Pubmed ID: 22415065

This study evaluated the breathing pattern of 30 obese patients [32±9 years old; body mass index (BMI): 42.72±4.10kg/m(2)] before and after bariatric surgery and compared them with 30 control individuals (31±8 years old, BMI: 21.99±2.22kg/m(2)). Measurements were performed using calibrated respiratory inductive plethysmography. Six months after bariatric surgery, obese patients exhibited a significant reduction in tidal volume (V(T)), minute ventilation (V(E)) and inspiratory duty cycle (T(I)/T(TOT)) compared with pre-surgical values. The control group had a higher breathing frequency, V(E) and phase angle (PhAng). There were no significant differences in V(T)/T(I), percentage of rib cage motion (%RC) or abdominal motion (%AB). Obese patients exhibited changes in their breathing pattern and asynchrony after bariatric surgery without any changes in thoracoabdominal motion. Certain aspects of the breathing pattern of obese patients became more similar to those of the controls after surgery.

Predictors of Right Ventricle Dysfunction After Anterior Myocardial Infarction

The Canadian Journal of Cardiology. Mar, 2012  |  Pubmed ID: 22421637

BACKGROUND: Regardless significant therapeutic advances, mortality and morbidity after myocardial infarction (MI) are still high. For a long time, the importance of right ventricle (RV) function has been neglected. Recently, RV dysfunction has also been associated with poor outcomes in the setting of heart failure. The shape, location, and contraction conditions make the RV chamber assessment technically challenging. METHODS: Our study identified clinical characteristics and left ventricle (LV) echocardiographic data performed 3-5 days after MI that could be associated with RV dysfunction (RV fractional area change [FAC] < 35%) 6 months after MI. RESULTS: The RV dysfunction group consisted of 11 patients (RV FAC 29.4% ± 5.2) and the no RV dysfunction group of 71 patients (RV FAC 43.7% ± 5.1); (P < 0.001). Both groups presented the same baseline clinical characteristics. Left atrium (LA), interventricular septum (IVS), and left ventricular posterior wall (LVPW) were larger in RV dysfunction than in no RV dysfunction. Conversely, E wave deceleration time (EDT) was lower in RV dysfunction when compared with no RV dysfunction. Left atrium(adj) (adjusted by gender, age, infarct size, and body mass index) (odds ratio [OR], 1.22; confidence interval [CI], 1.016-1.47; P = 0.032), interventricular septum(adj) (OR, 1.49; CI, 1.01-2.23; P = 0.044), and E wave deceleration time(adj) (OR, 0.98; CI, 0.97-0.98; P = 0.029) assessed soon after MI predicted RV failure after 6-months. CONCLUSIONS: LV diastolic dysfunction, resulting from anterior MI and assessed 3-5 days after the event, may play an important role in predicting RV dysfunction 6 months later.

The Role of C2 Domains in PKC Signaling

Advances in Experimental Medicine and Biology. 2012  |  Pubmed ID: 22453964

More than two decades ago, the discovery of the first C2 domain in conventional Protein Kinase Cs (cPKCs) and of its role as a calcium-binding motif began to shed light on the activation mechanism of this family of Serine/Threonine kinases which are involved in several critical signal transduction pathways. In this chapter, we review the current knowledge of the structure and the function of the different C2 domains in PKCs. The C2 domain of cPKCs is a calcium sensor and its calcium-dependent binding to phospholipids is crucial for kinase activation. While the functional role of the cPKC C2 domain is better understood, phylogenetic analysis revealed that the novel C2 domain is more ancient and related to the C2 domain in the fungal PKC family, while the cPKC C2 domain is first associated with PKC in metazoans. The C2 domain of novel PKCs (nPKCs) does not contain a calcium-binding motif but still plays a critical role in nPKCs activation by regulating C1-C2 domain interactions and consequently C2 domain-mediated inhibition in both the nPKCs of the epsilon family and the nPKCs of the delta family. Moreover, the C2 domain of the nPKCs of the delta family was shown to recognize phosphotyrosines in a novel mode different from the ones observed for the Src Homology 2 (SH2) and the phosphotyrosine binding domains (PTB). By binding to phosphotyrosines, the C2 domain regulates the activation of this subclass of PKCs. The C2 domain was also shown to be involved in protein-protein interactions and binding to the receptor for activated C-kinase (RACKs) thus contributing to the subcellular localization of PKCs. In summary, the C2 domain is a critical player that can sense the activated signaling pathway in response to external stimuli to specifically regulate the different conventional and novel PKC isoforms.

Ventilation Heterogeneity Predicts Asthma Control in Adults Following Inhaled Corticosteroid Dose Titration

The Journal of Allergy and Clinical Immunology. Mar, 2012  |  Pubmed ID: 22460065

BACKGROUND: Asthma guidelines recommend inhaled corticosteroid (ICS) dose titration for patients on the basis of an assessment of current asthma control. However, the physiological determinants of asthma symptom control are poorly understood and spirometry is a poor predictor of symptomatic response. OBJECTIVE: To determine the role of small airway measurements in predicting the symptom response following ICS dose titration. METHODS: Adult asthmatic patients had the Asthma Control Questionnaire (ACQ) scores and lung function measured at baseline and after 8 weeks. Tests included spirometry, plethysmography, sputum cell count, exhaled nitric oxide, airway hyperresponsiveness to mannitol, respiratory system mechanics using the forced oscillation technique, and ventilation heterogeneity using the multiple breath nitrogen washout. The parameters ventilation heterogeneity in convection-dependent airways and ventilation heterogeneity in diffusion-dependent airways were derived as measures of ventilation heterogeneity in the small airways. The dose of ICS was doubled if the ACQ score was greater than or equal to 1.5 (uptitration) and quartered if the ACQ score was less than 1.5 (downtitration). The relationships between baseline physiological parameters and the change in the symptom-only 5-item ACQ (deltaACQ-5) were examined by using Spearman correlations, forward stepwise linear regressions, and receiver operator curve analyses. RESULTS: ICS dose uptitration (n = 20) improved ACQ-5 scores (1.76 to 1.16; P = .04). Baseline fraction of exhaled nitric oxide (r = -0.55; P = .01) and ventilation heterogeneity in convection-dependent airways (r = -0.64; P = .002) correlated with deltaACQ-5, but ventilation heterogeneity in convection-dependent airways was the only independent predictor (r(2) = 0.34; P = 0.007). ICS dose downtitration (n = 41) worsened ACQ-5 scores (0.46 to 0.80; P < .001), with 29% of the patients having a deltaACQ-5 of greater than 0.5. Only baseline ventilation heterogeneity in diffusion-dependent airways correlated with deltaACQ-5 (r = 0.40; P = .009) and identified subjects with deltaACQ-5 of greater than 0.5 (receiver operator curve area under the curve = 0.78; P = .0003). CONCLUSIONS: Ventilation heterogeneity predicts symptomatic responses to ICS dose titration. Worse small airways function predicts symptomatic improvement to ICS dose uptitration and loss of symptom control during downtitration.

Longitudinal Study of Aortic Isthmus Doppler in Appropriately Grown and Small-for-gestational-age Fetuses with Normal and Abnormal Umbilical Artery Doppler

Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. Apr, 2012  |  Pubmed ID: 21674659

To establish reference ranges using longitudinal data for aortic isthmus (AoI) Doppler indices in appropriate-for-gestational-age (AGA) fetuses and to document the longitudinal trends in a cohort of small-for-gestational-age (SGA) fetuses with normal umbilical artery Doppler and in fetuses with intrauterine growth restriction (IUGR) and abnormal umbilical artery Doppler.

Pharmacokinetic Characterization of a Natural Product-inspired Novel MEK1 Inhibitor E6201 in Preclinical Species

Cancer Chemotherapy and Pharmacology. Jan, 2012  |  Pubmed ID: 21698359

E6201 is a natural product-inspired novel inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-1 (MEK1) and other kinases and is currently under development as an anticancer (parenteral administration) and antipsoriasis agent (topical application). In vitro and in vivo preclinical studies were performed to characterize the pharmacokinetics of E6201. Allometric scaling was applied to predict human pharmacokinetics of E6201.

Effects of Exercise Intensity on Rating of Perceived Exertion During a Multiple-set Resistance Exercise Session

Journal of Strength and Conditioning Research / National Strength & Conditioning Association. Feb, 2012  |  Pubmed ID: 22233796

The aim of this study was to analyze the effects of intensity on rating of perceived exertion (RPE) during a multiple-set resistance exercise session. Fourteen men (22.9 ± 3.8 years) with previous experience in resistance training (22.9 ± 3.8 years) performed 2 experimental sessions in random order: resistance exercise at 50% of 1 repetition maximum (1RM) (E50%) and resistance exercise at 70% of 1RM (E70%). In both sessions, 5 exercises (bench press, bent-over row, frontal raises, arm curl, and overhead triceps extension) were performed in 3 sets of 12, 9, and 6 repetitions, respectively. Active muscle RPEs were measured after each repetition using the OMNI-Resistance Exercise Scale (OMNI-RES). In the 3 sets of 5 exercises, the RPE was higher at E70% than that at E50%. The differences in RPE between intensities were observed in both the first and the sixth repetitions for each exercise. In the E70% session, the RPE increased between sets in all exercises, whereas it did not change in the E50% session. In conclusion, the RPE was higher at 70% of 1RM than that at 50% of 1RM. Moreover, in a multiple-set prescription, the RPE did not change between sets with 50% of 1RM, whereas the RPE increased between sets with 70% of 1RM. These findings suggest that RPE can be effectively used to prescribe and monitor resistance exercise intensity during an entire multiple-set exercise session in young men with previous experience in resistance training.

Digital Interactive Learning of Oral Radiographic Anatomy

European Journal of Dental Education : Official Journal of the Association for Dental Education in Europe. Feb, 2012  |  Pubmed ID: 22251358

Studies reporting high number of diagnostic errors made from radiographs suggest the need to improve the learning of radiographic interpretation in the dental curriculum. Given studies that show student preference for computer-assisted or digital technologies, the purpose of this study was to develop an interactive digital tool and to determine whether it was more successful than a conventional radiology textbook in assisting dental students with the learning of radiographic anatomy.

Latin America and Larry Yannuzzi

Retina (Philadelphia, Pa.). Feb, 2012  |  Pubmed ID: 22270775

Classical Reactive Molecular Dynamics Implementations: State of the Art

Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry. Apr, 2012  |  Pubmed ID: 22287184

Reactive molecular dynamics (RMD) implementations equipped with force field approaches to simulate both the time evolution as well as chemical reactions of a broad class of materials are reviewed herein. We subdivide the RMD approaches developed during the last decade as well as older ones already reviewed in 1995 by Srivastava and Garrison and in 2000 by Brenner into two classes. The methods in the first RMD class rely on the use of a reaction cutoff distance and employ a sudden transition from the educts to the products. Due to their simplicity these methods are well suited to generate equilibrated atomistic or material-specific coarse-grained polymer structures. In connection with generic models they offer useful qualitative insight into polymerization reactions. The methods in the second RMD class are based on empirical reactive force fields and implement a smooth and continuous transition from the educts to the products. In this RMD class, the reactive potentials are based on many-body or bond-order force fields as well as on empirical standard force fields, such as CHARMM, AMBER or MM3 that are modified to become reactive. The aim with the more sophisticated implementations of the second RMD class is the investigation of the reaction kinetics and mechanisms as well as the evaluation of transition state geometries. Pure or hybrid ab initio, density functional, semi-empirical, molecular mechanics, and Monte Carlo methods for which no time evolution of the chemical systems is achieved are excluded from the present review. So are molecular dynamics techniques coupled with quantum chemical methods for the treatment of the reactive regions, such as Car-Parinello molecular dynamics.

Involvement of P53 in Gemcitabine Mediated Cytotoxicity and Radiosensitivity in Breast Cancer Cell Lines

Gene. May, 2012  |  Pubmed ID: 22353361

Gemcitabine (2',2'-difluoro-2'-deoxycytidine; dFdCyd) is one of the anti-metabolites drugs that target DNA replication. We evaluated dFdCyd cytotoxicity and its radiosensitizing ability in human breast cancer cell lines, MCF-7 (wild-type p53) and MDA-MB-231 (mutant-type p53) along with normal mammary epithelial cell line (MCF-12) for comparison. Radiosensitivity and cytotoxicity were measured by the clonogenic survival assays. DNA DSBs was studied by Pulse Field Gel Electrophoresis (PFGE) and cell cycle distribution was analyzed by flow cytometry. MDA-MB-231 cells were the most sensitive to the cytotoxicity of dFdCyd (IC(50) 5nM) then MCF-7 (IC(50) 10nM), whereas MCF-12 cells were the most resistant to the cytotoxicity of dFdCyd (IC(50) 70nM). MCF-12 and MCF-7 cell lines did not show any radiosensitization to dFdCyd, whereas the MDA-MB-231 cells showed significantly increased radioresistant to dFdCyd at equimolar concentration (p=0.002) and at IC(50) concentration (p<0.001). The DNA double strand breaks (DSBs) repair showed that dFdCyd neither increases DNA DSBs nor decreases the rate of their repair in MCF-12 and MCF-7 cell lines, while the same treatment in MDA-MB-231 cell line led to decrease the rate of DSBs or increase the rate of DNA repair (p=0.034). Therefore, dFdCyd is a cytotoxic agent, especially in the cancer cells irrespective of having wild-type or mutated p53 protein, but it is not effective as radiosensitizer in the cell lines used in this study. dFdCyd combined with radiation reduces the efficacy of chemo-radiotherapy in p53 mutated cells. Therefore, p53-mutated cancer could be a counter-indication for radiation-gemcitabine combined treatment.

Environmental Risks to Public Health in the United Arab Emirates: A Quantitative Assessment and Strategic Plan

Environmental Health Perspectives. Feb, 2012  |  Pubmed ID: 22357098

Background: Environmental risks to health in the United Arab Emirates (UAE) have shifted rapidly from infectious to noninfectious diseases as the nation has developed at an unprecedented rate. In response to public concerns over newly emerging environmental risks, the Environment Agency-Abu Dhabi commissioned a multi-disciplinary environmental health strategic planning project. Objectives: The objectives were to quantify the illnesses and premature deaths in the UAE attributable to 14 environmental pollutant categories; prioritize these 14 risk factors; and identify interventions. Methods: We estimated the disease burden imposed by each risk using an attributable fraction approach, and we prioritized the risks using an empirically tested stakeholder engagement process. We engaged government personnel, scientists, and other stakeholders to identify interventions. Results: The UAE's environmental disease burden is low by global standards. Ambient air pollution is the leading contributor to premature mortality (approximately 650 annual deaths, 95% CI: 140-1400). Risks leading to more than 10,000 annual healthcare facility visits include occupational exposures, indoor air pollution, drinking water contamination, seafood contamination, and ambient air pollution. On average, UAE stakeholders ranked outdoor air pollution as the highest priority (mean rank 1.4, 95% range 1-2) and indoor air pollution as the second-highest priority (mean rank 3.3, 95% range 1-8) among the 14 risks considered. The resulting strategic plan identifies 216 potential interventions for reducing environmental risks to health. Conclusions: The strategic planning exercise described here provides a framework for systematically deciding how to invest public funds to maximize expected returns in environmental health-where returns are measured in terms of reductions in a population's environmental burden of disease.

The Lateral Thoracic Nerve and the Cutaneous Maximus Muscle-A Novel in Vivo Model System for Nerve Degeneration and Regeneration Studies

Experimental Neurology. Feb, 2012  |  Pubmed ID: 22361024

We report a novel in vivo mouse model system to study regeneration of injured motor nerve and spatiotemporal pattern of denervation in experimental nerve diseases. The lateral thoracic nerve (LTN), as a pure motor nerve, innervates the cutaneous maximus muscle (CMM) by some of the shortest and the longest motor nerve fibers in the mouse body. Its branches and nerve terminals can be imaged in whole mount preparations. Here we describe the branching pattern of the LTN and its innervation of the CMM, and characterize degeneration and regeneration over time after a LTN crush by morphological and electrophysiological analyses. We demonstrate the utility of this model in a well-established neurotoxicity paradigm and in a genetic disease model of the peripheral neuropathy. Furthermore, this system enables punch biopsies that allow repeated and multi-location examinations for LTN regeneration and CMM reinnervation over time. The presence of the LTN and the CMM in a variety of species and its easy accessibility suggests that this in vivo model system offers considerable promise for future nerve degeneration and regeneration research.

Drug Eluting Stents: Developments and Current Status

Journal of Controlled Release : Official Journal of the Controlled Release Society. Feb, 2012  |  Pubmed ID: 22366546

Coronary stenting has revolutionized current perspective of coronary artery disease management. Bare-metal stents (BMS) were introduced in 1994, but long-term results have been shattered by the dual problems of in-stent restenosis (ISR) and stent thrombosis associated with BMS. Though stent thrombosis became much less frequent after the introduction of antiplatelet therapy, restenosis however remained as a significant problem. Intense work on stent development has successfully led to the introduction of drug-eluting stents (DES) in 2002, as an effort to address restenosis problem. First generation DES (sirolimus and paclitaxel eluting) were introduced first and found to be more effective than BMS. The use of first generation DES dealt with the problem of restenosis. But, despite early successes, uncertainty remains on the overall safety, especially for late adverse clinical events such as stent thrombosis. Thus, the second generation (everolimus and zotarolimus eluting) stents were developed and introduced with lower thrombosis rates. Today, in the search for improving the performance of available DES various developments and clinical studies are ongoing. Research and developments is primarily centred on increasing the long-term safety and efficacy of stents.

Parathyroid Hormone, A Crucial Mediator of Pathologic Cardiac Remodeling in Aldosteronism

Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. Feb, 2012  |  Pubmed ID: 22373564

Aldosteronism, or chronic elevation in plasma aldosterone (ALDO) (inappropriate for dietary Na(+) intake), is accompanied by an adverse structural remodeling of the heart and vasculature. Herein, we bring forward a new perspective in which parathyroid hormone (PTH) is identified as a crucial mediator of pathologic cardiac remodeling in aldosteronism. Secondary hyperparathyroidism (SHPT) appears because of the marked urinary and fecal losses of Ca(2+) and Mg(2+) that accompany aldosteronism which creates ionized hypocalcemia and hypomagnesemia, providing major stimuli to the parathyroids' enhanced secretion of PTH. Invoked to restore extracellular Ca(2+) and Mg(2+) homeostasis, elevations in plasma PTH lead to paradoxical intracellular Ca(2+) overloading of diverse tissues. In the case of cardiomyocytes, the excessive intracellular Ca(2+) accumulation involves both cytosolic free and mitochondrial domains with a consequent induction of oxidative stress by these organelles and lost ATP synthesis. The ensuing opening of their inner membrane permeability transition pore (mPTP) accounts for the osmotic swelling and structural degeneration of mitochondria followed by programed cell necrosis. Tissue repair, invoked to preserve the structural integrity of myocardium accounts for a replacement fibrosis, or scarring, which is found scattered throughout the right and left heart; it represents a morphologic footprint of earlier necrosis. Multiple lines of evidence are reviewed that substantiate the PTH-mediated paradigm and the mitochondriocentric signal-transducer-effector pathway to cardiomyocyte necrosis.

Unmet Challenges in Cancer Disparities--letter

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. Jan, 2012  |  Pubmed ID: 22144498

Calcium Binding to Leptospira Outer Membrane Antigen LipL32 is Not Necessary for Its Interaction with Plasma Fibronectin, Collagen Type IV, and Plasminogen

The Journal of Biological Chemistry. Feb, 2012  |  Pubmed ID: 22147698

LipL32 is the most abundant outer membrane protein from pathogenic Leptospira and has been shown to bind extracellular matrix (ECM) proteins as well as Ca(2+). Recent crystal structures have been obtained for the protein in the apo- and Ca(2+)-bound forms. In this work, we produced three LipL32 mutants (D163-168A, Q67A, and S247A) and evaluated their ability to interact with Ca(2+) and with ECM glycoproteins and human plasminogen. The D163-168A mutant modifies aspartate residues involved in Ca(2+) binding, whereas the other two modify residues in a cavity on the other side of the protein structure. Loss of calcium binding in the D163-D168A mutant was confirmed using intrinsic tryptophan fluorescence, circular dichroism, and thermal denaturation whereas the Q67A and S247A mutants presented the same Ca(2+) affinity as the wild-type protein. We then evaluated if Ca(2+) binding to LipL32 would be crucial for its interaction with collagen type IV and plasma proteins fibronectin and plasminogen. Surprisingly, the wild-type protein and all three mutants, including the D163-168A variant, bound to these ECM proteins with very similar affinities, both in the presence and absence of Ca(2+) ions. In conclusion, calcium binding to LipL32 may be important to stabilize the protein, but is not necessary to mediate interaction with host extracellular matrix proteins.

Economic Evaluation of a 100% Whey-based Partially Hydrolyzed Infant Formula in the Prevention of Atopic Dermatitis Among Swiss Children

Journal of Medical Economics. 2012  |  Pubmed ID: 22171935

Abstract Objective: A pharmacoeconomic analysis was undertaken to determine costs, consequences, and cost-effectiveness of a partially hydrolyzed 100% whey-based infant formula, NAN-HA®, manufactured by Nestlé S.A, Switzerland (PHF-W), branded under BEBA HA® in Switzerland, in the prevention of atopic dermatitis (AD) in 'at risk' Swiss children when compared to standard cow's milk formula (SF). Methods: Based on a 12-month time horizon including 6 months of formula consumption, an economic model was developed synthesizing treatment pathways, resource utilization, and costs associated with the treatment of AD in healthy 'at risk' Swiss newborns who could not be exclusively breastfed. Model inputs were retrieved from the literature, official formularies, and expert opinion. The treatment pathways considered a medical treatment approach, supplemented in some instances by a change of formula. The final outcome was the expected cost per avoided case of AD, yielding an incremental cost effectiveness ratio (ICER) for PHF-W vs SF. Outcomes were presented from three perspectives: the Swiss public healthcare system (MOH), the subject's family, and society (SOC). A secondary analysis compared PHF-W to whey-based extensively hydrolyzed formula (EHF) in prevention. Results: The model yielded 1653 avoided AD cases by selecting PHF-W over SF in a birth cohort of 22,933 'at risk' infants. The base case analyses generated an expected ICER of CHF 982 from the MOH perspective as well as savings of CHF 2202 and CHF 1220 from the family and SOC perspectives, respectively. PHF-W yielded CHF 11.4M savings against EHF when the latter was assumed to be used in prevention. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. Conclusion: Under a range of assumptions, this analysis has established the dominance from the family and societal perspectives and cost-effectiveness from the MOH perspective of PHF-W vs SF in the prevention of AD among 'at risk' Swiss infants.

Economic Evaluation of a 100% Whey-based Partially Hydrolyzed Infant Formula in the Prevention of Atopic Dermatitis Among Danish Children

Journal of Medical Economics. 2012  |  Pubmed ID: 22171936

Abstract Objective: A pharmacoeconomic analysis was undertaken to determine costs, consequences, and cost-effectiveness of a brand of partially hydrolyzed 100%-whey formula manufactured by Nestlé (PHF-W), in the prevention of atopic dermatitis (AD) in 'at risk' Danish children compared to extensively hydrolyzed formula (EHF-Whey or Casein). Methods: Given the non-significant differences between PHF-W and EHF, the base case analytic approach amounted to a cost-minimization analysis (CMA) reporting the difference in formula acquisition costs over the period of formula consumption for the population of interest. However, sensitivity analyses (SAs) were undertaken to explore applying the nominal efficacy of PHF-W and EHF, thus leading to a cost-effectiveness analysis (CEA). Hence, an economic model based on a 12-month time horizon was developed synthesizing treatment pathways, resource utilization, and costs associated with the treatment of AD in the population of interest. The final economic outcome of the SAs was the incremental cost per avoided case (ICER) defined as the expected cost per avoided case of AD for PHF-W vs EHF, determined from three perspectives: the Ministry of Health (MOH), the family of the subject, and society (SOC). Results: In the base case CMA, savings of DKK 9 M, DKK 20 M, and DKK 29 M were generated for PHF-W vs EHF from the MOH, family, and SOC perspectives. In the sensitivity CEA, PHF-W was dominant over EHF-Whey from all perspectives, while EHF-Casein displayed against PHF-W unattractive ICERs of DKK 315,930, DKK 408,407, and DKK 724,337 from the MOH, family, and SOC perspectives. Probabilistic SAs indicated that PHF-W was 86% likely to be dominant over EHF-Whey, whereas EHF-Casein had no likelihood of dominating PHF-W. Conclusion: Under a range of assumptions, this analysis demonstrated the attractiveness of PHF-W vs both types of EHF in the prevention of AD among 'at risk' Danish infants who are not or cannot be exclusively breastfed.

Maternal Mortality and the Rising Cesarean Rate

International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. Feb, 2012  |  Pubmed ID: 22119498

To review maternal mortality in a large stand-alone maternity hospital in a European city and to determine whether the increased cesarean rate was associated with an increase in maternal deaths.

Spectral-domain Optical Coherence Tomography in Patients with Commotio Retinae

Retina (Philadelphia, Pa.). Apr, 2012  |  Pubmed ID: 22105503

: To describe the morphologic characteristics of commotio retinae using spectral-domain optical coherence tomography and to evaluate its utility in prognosis and follow-up.

Clinical Expert Consensus Statement on Best Practices in the Cardiac Catheterization Laboratory: Society for Cardiovascular Angiography and Interventions

Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. Mar, 2012  |  Pubmed ID: 22434598

Analysis of Three Xanthomonas Axonopodis Pv. Citri Effector Proteins in Pathogenicity and Their Interactions with Host Plant Proteins

Molecular Plant Pathology. Mar, 2012  |  Pubmed ID: 22435635

Xanthomonas axonopodis pv. citri, the bacterium responsible for citrus canker, uses effector proteins secreted by a type III protein secretion system to colonize its hosts. Among the putative effector proteins identified for this bacterium, we focused on the analysis of the roles of AvrXacE1, AvrXacE2 and Xac3090 in pathogenicity and their interactions with host plant proteins. Bacterial deletion mutants in avrXacE1, avrXacE2 and xac3090 were constructed and evaluated in pathogenicity assays. The avrXacE1 and avrXacE2 mutants presented lesions with larger necrotic areas relative to the wild-type strain when infiltrated in citrus leaves. Yeast two-hybrid studies were used to identify several plant proteins likely to interact with AvrXacE1, AvrXacE2 and Xac3090. We also assessed the localization of these effector proteins fused to green fluorescent protein in the plant cell, and observed that they co-localized to the subcellular spaces in which the plant proteins with which they interacted were predicted to be confined. Our results suggest that, although AvrXacE1 localizes to the plant cell nucleus, where it interacts with transcription factors and DNA-binding proteins, AvrXacE2 appears to be involved in lesion-stimulating disease 1-mediated cell death, and Xac3090 is directed to the chloroplast where its function remains to be clarified.

USE OF LUTEIN AND ZEAXANTHIN ALONE OR COMBINED WITH BRILLIANT BLUE TO IDENTIFY INTRAOCULAR STRUCTURES INTRAOPERATIVELY

Retina (Philadelphia, Pa.). Mar, 2012  |  Pubmed ID: 22450514

PURPOSE: To determine whether a natural dye solution based on lutein and zeaxanthin alone or combined with Brilliant Blue stains and facilitates peeling of intraocular membranes in human eyes. METHODS: In this study of 60 cadaveric eyes, open-sky vitrectomy including posterior hyaloid detachment was performed. Different lutein and zeaxanthin concentrations (0.01-20%) were tested alone or combined with different Brilliant Blue concentrations (0.0125-0.025%) in the corneal endothelium, corneal epithelium, anterior and posterior capsule, vitreous cavity through the macula including the posterior hyaloid, and internal limiting membrane. The various dye solutions were in contact with the intraocular membranes for <1 minute and then were removed by mechanical aspiration or membrane peeling initiated and completed with intraocular forceps. The specimens were examined by light and electron transmission microscopy. RESULTS: Contact between lutein and zeaxanthin and the retinal, lens, and vitreous surface resulted in orange and greenish staining of the intraocular membranes, which facilitated surgical steps in all eyes. Lutein and zeaxanthin alone was useful for vitreous identification and lutein and zeaxanthin combined with Brilliant Blue had strong affinity for internal limiting membrane and anterior capsule. Light microscopy confirmed internal limiting membrane removal in all eyes tested. No dye solutions remained in the eyes after the membrane removal. CONCLUSION: A natural dye solution based on lutein and zeaxanthin alone or combined with Brilliant Blue efficiently stained the anterior capsule, vitreous, and internal limiting membrane in human cadaveric eyes and may be a useful tool for vitreoretinal or cataract surgery.

Surface Plasmon Mapping of Dumbbell-Shaped Gold Nanorods: The Effect of Silver Coating

Langmuir : the ACS Journal of Surfaces and Colloids. Mar, 2012  |  Pubmed ID: 22452636

We report on the identification of surface plasmons in individual gold dumbbell-shaped nanoparticles (AuDBs), as well as AuDBs coated with silver. We use spatially resolved electron energy-loss spectroscopy in a scanning electron microscope, which allows us to map plasmon-energy and intensity spatial distributions. Two dominant plasmon resonances are ex-perimentally resolved in both AuDBs and silver-coated AuDBs. The intensity of these features is peaked either at the tips or at the sides of the nanoparticles. We present boundary element method simulations in good agreement with the ex-periment, allowing us to elucidate the nature of such modes. While the lower-energy, tip-focused plasmon is of longitudinal character for all dumbbells under consideration, the second side-bound plasmon has a more involved symmetry, starting as a longitudinal quadrupole in homogeneous AuDBs and picking up transversal components when silver coating is added. The longitudinal dipolar mode energy is found to blue-shift upon coating with silver. We find that the substrate produces size-able shifts in the plasmons of silver-coated AuDBs. Our analysis portraits a complex plasmonic scenario in metal nanoparti-cles coated with silver, including a transition from the original homogeneous gold dumbbell plasmons to the modes of ho-mogeneous silver rods. We believe that these findings can have potential application to plasmon engineering.

Thromboprophylaxis for Women Undergoing Caesarean Section

Irish Medical Journal. Feb, 2012  |  Pubmed ID: 22455243

Thromboprophylaxis for women undergoing caesarean section (CS) was introduced in the hospital in 1995. This study audited the use of tinzaparin prophylaxis in a nested cohort of women who screened negative for diabetes mellitus at 28 weeks gestation. All the women had their weight measured and BMI calculated at the first antenatal visit. Of the 284 women, 68 (24%) had a CS and all received tinzaparin. Of the 68, however, 94% received a dose lower than recommended. Compliance with prophylaxis was complete but compliance with the recommended dosage was suboptimal, which may result in venous thromboembolism after CS despite thromboprophylaxis.

Surface Crystallization of Rapamycin on Stents Using a Temperature Induced Process

Langmuir : the ACS Journal of Surfaces and Colloids. Mar, 2012  |  Pubmed ID: 22462404

Metallic drug eluting stents (DES) are usually prepared by coating with a drug-polymer matrix as a rate controlling diffusion barrier. But, coating materials may display numerous problems, thus carrier free DES are desired, yet releasing drug over long period of time. For this, we are reporting a novel temperature induced (TI) crystallization process for coating rapamycin on stents. Rapamycin crystals with a defined morphology and target drug load were applied from supersaturated solution. This method enables fabrication of controllable and homogeneous crystalline coatings on stent scaffolds and allowing the drug to release for several weeks.

Analyzing Spatial and Temporal (222)Rn Trends in Maine

Health Physics. Feb, 2012  |  Pubmed ID: 22217584

Prolonged radon exposure has been linked to lung cancer. Cancer registry data indicates excess risk for age-adjusted lung cancer in Maine. Maine's mean residential radon activity exceeds the EPA maximum contaminant level (MCL). This paper describes the application of spatial autocorrelation methods to retrospective data as a means of analyzing radon activity in Maine. Retrospective air and well water radon activity data, sampled throughout Maine between 1993 and 2008, are standardized and geocoded for analysis. Three spatial autocorrelation algorithms-local Getis-Ord, local Moran, and spatial scan statistic-are used to identify spatial, temporal, and spatiotemporal radon activity clusters and/or outliers. Spatial clusters of high air- and well water-Rn activity are associated with Maine's Lucerne and Sebago granitic formations. Spatial clusters of low air- and well water-Rn activity are associated with Biddeford Granite and the metamorphic bedrock formation Silurian Ordovician Vassalboro. Space-time analysis indicates that most spatial clusters persist over the period of sampling. No significant temporal clusters are identified. Persistent spatial variations in radon may help to better understand and predict radon-related health risks associated with Maine residences.

The Role of the Small Airways in the Clinical Expression of Asthma in Adults

The Journal of Allergy and Clinical Immunology. Feb, 2012  |  Pubmed ID: 22188824

The clinical relevance of increased ventilation heterogeneity, a marker of small-airways disease, in asthmatic patients is unclear. Ventilation heterogeneity is an independent determinant of airway hyperresponsiveness (AHR), improves with bronchodilators and inhaled corticosteroids (ICSs), and worsens during exacerbations, but its relationship to asthma control is unknown.

The Effects of Green Tea Consumption on Cardiometabolic Alterations Induced by Experimental Diabetes

Experimental Diabetes Research. 2012  |  Pubmed ID: 22474420

We evaluated cardiac autonomic modulation by heart rate (HRV), and arterial pressure variability (APV), and metabolic response in streptozotocin diabetic rats treated with green tea. Male Wistar rats were separated in groups: control, drinking tap water (C), green tea-treated (GT) group, diabetic, drinking tap water (D), and diabetic, treated with green tea (DGT). Kidney mass was greater in D and DGT than in C and GT, but reduced in DGT compared to D. Green tea prevented the increase in creatinine clearance and reduced hyperglycemia in DGT compared to D. Arterial pressure was increased in GT and decreased in D compared to C. HRV was reduced in D compared with all groups. APV was decreased in D compared to C and recovery in DGT. Sympathetic modulation of APV was decreased in D compared with all groups. Green tea reduced hyperglycemia, prevented renal injury and autonomic dysfunction, suggesting reduced cardiovascular risk and target organ damage in diabetes.

Electrocatalytic Properties of Prussian Blue Nanoparticles Supported on Poly(m-aminobenzenesulphonic Acid)-functionalised Single-walled Carbon Nanotubes Towards the Detection of Dopamine

Colloids and Surfaces. B, Biointerfaces. Mar, 2012  |  Pubmed ID: 22475526

Edged plane pyrolytic graphite electrode (EPPGE) was modified with and without Prussian blue (PB) nanoparticles and polyaminobenzene sulphonated single-walled carbon nanotubes (SWCNTPABS) using the chemical deposition method. The electrodes were characterised using microscopy, spectroscopy and electrochemical techniques. Results showed that edged plane pyrolytic graphite-single-walled carbon nanotubes-prussian blue (EPPGE-SWCNT-PB) electrode gave the best dopamine (DA) current response, which increases with increasing PB layers. The catalytic rate constant of 1.69×10(5)mol(-1)cm(3)s(-1), Tafel value of 112mVdec(-1), and limit of detection of DA (2.8nM) were obtained. Dopamine could be simultaneously detected with ascorbic acid. The electrode was found to be electrochemically stable, reusable and can be used for the analysis of DA in real drug samples.

Lithium and Oxidative Stress Lessons from the MPTP Model of Parkinson's Disease

Neuroscience Letters. Mar, 2012  |  Pubmed ID: 22480690

Lithium has been successfully employed therapeutically for treatment of bipolar depressive illness; however, its mechanism of action is poorly understood. Recently, it has been demonstrated by us that lithium can prevent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) dopaminergic neurotoxicity in mice. From analyzing the pattern of protection in various parameters, we suggest that lithium protects against MPTP-induced depletion of striatal dopamine (DA) by preventing free radical-induced inactivation of tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine synthesis. Possible neuroprotective effect of lithium against H(2)O(2)-induced cell death was assessed in human neuroblastoma; SH-SY5Y cell line. Pretreatment with LiCl (2mM and 4mM) for 7 days protected against H(2)O(2) neurotoxicity in a dose-dependent manner. However, this protection could not be achieved through short-term incubation with LiCl. In agreement; we found that lithium lacks immediate antioxidant activity using the in vitro lipid peroxidation essay indicating that not acute but chronic treatment with lithium allows cells to deal better with oxidative stress.